PANCREATIC CANCER MATTERS - Immunology Research A Collaboration with the Bloomberg Kimmel Institute for Cancer Immunotherapy - Johns Hopkins Medicine
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ISSUE NO. 2 | 2017/2018
THE JOH NS H OP KIN S KI MME L C ANC E R C E N T E R
PANCREATIC CANCER
MATTERS
Immunology
Research
A Collaboration with the
Bloomberg~Kimmel Institute
for Cancer Immunotherapy
Stefanie Joho,
immunotherapy patient
2 Decades of Immunology
Research Pays Off
Many new opportunities to pursue
Elizabeth Jaffee has devoted her entire career to figuring out how to engage the
immune system against cancer, particularly pancreatic cancer. Her work led to the first
therapeutic cancer vaccine, known as GVAX. It recruited vital immune killer T cells to
pancreatic tumors in force.This in and of itself was a victory because historically, pancreatic
cancers did not attract the attention of the immune system.
I
n April 1997, Jaffee and colleagues
reported that GVAX awakened the
immune system. It was considered a
pioneering breakthrough—one of the
few in cancer immunology. It occurred
in an environment of promising findings
that were frequently dashed in the clinic.
The vaccine approach—developed
almost a decade earlier by Jaffee, Drew
Pardoll and Hyam Levitsky—was a rare
immunology success story. It proved that
the immune system could be coaxed to
mobilize against cancer.
Jaffee and colleagues’ vaccine had
overcome a major barrier, and these
cells—manufactured by our own body
and immensely more powerful than any
anticancer drug—were seeking out the
From left, front row, Lei Zheng, Eric Lutz and Elizabeth Jaffee, and the rest of the research team
cancer. In some patients, that was all that
was needed to provide unprecedented
and long-lasting control of their Jaffee and colleagues stayed the course, Jaffee’s body of work earned her
pancreatic cancer. In many patients, convinced that, in time, they would “IMMUNE CELLS WERE BEING superstar status in the world of cancer
however, the vaccine had no effect. Jaffee, unlock the clues that could make the DUPED. THEY WERE ESSENTIALLY immunology and pancreatic cancer
clinical partner Dan Laheru, a host immune system the perfect weapon to research. She is an associate director of
fight cancer. Jaffee and Laheru recruited BEING TOLD, ‘GO HOME.THERE IS the new Bloomberg~Kimmel Institute
of talented young scientists and their
philanthropic partners worked tirelessly the best and brightest minds. Laheru NOTHING TO SEE HERE.’ ” for Cancer Immunotherapy at Johns
and collaboratively with other Kimmel led the clinical research, and young –BOB ANDERS Hopkins, formed last March to speed
Cancer Center experts to decipher the Daniel Laheru, M.D., the Ian T. MacMillan Professor in Clinical Pancreatic Cancer investigators Dung Le, Eric Lutz and the translation of cancer immunology
“Immune cells were being duped.
components of the immune system that Research, and Elizabeth Jaffee, M.D., the Dana and Albert “Cubby” Broccoli Lei Zheng helped Jaffee make progress. discoveries into new therapies. She was
Professor of Oncology. Jaffee and Laheru are co-directors of the Skip Viragh Center
They were essentially being told, ‘Go
were preventing the T cells from doing This relentless determination paid off. The chosen to lead the Stand Up To Cancer-
for Pancreatic Cancer Clinical Research and Patient Care. home. There is nothing to see here,’” says
their job. discovery that cancer cells were corrupting Lustgarten Foundation Pancreatic Cancer
pathologist Bob Anders.
It took another decade for Jaffee and a natural regulatory process used to shut Convergence Dream Team to transform
normal cells that they foiled the immune system. Still, immune cell recognition of The process was dubbed immune
this collaborative team to reveal how down the immune response when its job pancreatic cancer into a treatable
system. That certainly played a role, the cancer most often did not translate tolerance. Jaffee and her immunology
cancers could grow and spread without was done created a new paradigm. In disease. She was also honored with the
Jaffee and other experts would learn as into an immune attack against the cancer. colleagues now realized that it wasn’t
attracting the attention of the immune cancer, this important and necessary “off 20th annual American Association for
they recognized that cancers with many The game changer occurred through enough to get the immune system to
system. There were many ideas. switch” was being used to shut down T Cancer Research Joseph H. Burchenal
gene mutations—setting them apart diligence. While many experts abandoned recognize the cancer. They would also
Cancers, which originate from normal cells, making them think their job was Award for Outstanding Achievement in
from normal cells—were the most likely the field of cancer immunology, daunted have to disrupt cancer’s ability to suppress
cells gone awry, were perhaps so similar to done before they ever took action against Clinical Cancer Research for her basic
to attract the attention of the immune by the complexity of the immune cell, the immune system.
the cancer. science and clinical contributions to
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cancer immunology. Her most recent Viragh Center so unique. “We cannot
accolade was her selection by Vice “SKIP’S GENEROSITY ALLOWED US overstate the importance and impact
President Joe Biden as co-chair of his that Skip has made—and continues to
Cancer Moonshot Blue Ribbon Panel. TO BUILD THIS PREMIER PROGRAM. make—on pancreatic cancer research and
She was the obvious choice, as Jaffee had NOW, WE MUST EMBARK ON THE treatment,” says Jaffee. “It allowed us to
already created the model Vice President NEXT PHASE, USING THE TOOLS integrate the basic science and clinical
Biden envisioned for his moonshot, expertise to provide the best and most
one that reflected cooperation among WE’VE CREATED AND DISCOVERIES innovative care to patients.”
academia, government, the private sector WE HAVE MADE OVER THE LAST With Viragh funding, Jaffee and
and philanthropy to translate cancer Laheru hired nurse practitioner and
immunology research into new therapies DECADE TO HELP EVEN MORE immune therapy expert Barbara
for patients. To bring cancer vaccines to PATIENTS.THIS CAN ONLY BE Biedrzycki to oversee patient care. “She
patients, Jaffee became an expert in FDA ACCOMPLISHED WITH ADDITIONAL is one of the few cancer nursing leaders in
regulations and vaccine manufacturing, the world, and she has played a vital role
opening a Good Manufacturing Practices RESEARCH.” –DANIEL LAHERU in increasing the patient volume in our Linda Rubin
facility at the Kimmel Cancer Center to clinic, particularly patients with advanced
make the vaccine. cancer and extend the benefit to many pancreatic cancer who have very few
Jaffee’s laboratory was a beacon of more patients. treatment options,” says Laheru. cancer into the bright world of survival.”
hope for those diagnosed with pancreatic Since opening, the clinic has seen more Mark Yarchoan was selected as the
cancer—one of the most dreaded The Viragh Difference than 2,000 pancreatic cancer patients. inaugural Linda Rubin Fellow. Jaffee and
forms of cancer and one for which few One of those patients who sought the It continues to expand and will move to Laheru will mentor him as he explores the
therapeutic advances had been made. The expertise of Jaffee and Laheru was Skip the new Skip Viragh Outpatient Cancer benefit of combination immune therapies
Whipple procedure, the primary—and Viragh. Viragh was a mutual fund Building upon its completion in the and, specifically, whether the addition
potentially curative—surgical treatment investment leader whose life was cut fall of 2017 (see story on page 14). This of immune checkpoint inhibitors can
for pancreatic cancer, was also perfected short in 2003 by pancreatic cancer. new facility is funded entirely by private increase the effectiveness of the pancreatic
at Johns Hopkins. For patients who Before his death, Viragh established the donations, including a $65 million gift cancer vaccine.
could not be cured with surgery, however, Viragh Family Foundation and cemented from Viragh’s foundation, and offers “The opportunity for aspiring investi-
Jaffee’s pancreatic cancer vaccine offered his mission to ensure a better future for the potential to double the number gators to work with senior faculty mem-
the possibility to hold the cancer in check. patients fighting pancreatic cancer. A of patients seen. A floor dedicated to bers at the Kimmel Cancer Center has al-
Patients like Kathleen Dowell, now $20 million initial investment in 2009 immune therapy for pancreatic cancer and lowed our program to consistently attract
a 20-year survivor, and Donna Bender, established the Skip Viragh Center for other gastrointestinal cancers will allow the most gifted young physician-scientists
a 12-year survivor, sought out Jaffee Pancreas Cancer Clinical Research and the latest immunotherapy discoveries from around the globe,” says Laheru. “The
and Laheru after being told they had Patient Care. The Skip Viragh Center to be moved to patient care in the most best way we can honor Linda is to develop
only months to live when their cancers allowed the Kimmel Cancer Center advanced clinical setting. better treatments for pancreatic cancer,
progressed after surgery, chemotherapy to accelerate clinical research, expand “Skip’s generosity allowed us to build and the fellowship she established makes
and radiation therapy. “Dr. Laheru the number of patients treated and, this premier program. Now, we must that possible.”
and my nurse, Beth Onners, were through Viragh-funded scholars, increase embark on the next phase, using the tools
the number of scientists dedicated to Young Investigators
as determined as I was to take on this we’ve created and discoveries we have “The progress we’ve made—which
cancer,” says Bender. “I am thankful for the understanding and treatment of made over the last decade to help even
pancreatic cancer. The Skip Viragh Center has only been possible because of the
the chance they gave me.” more patients,” says Laheru. “This can generosity of others—helps us attract Stefanie Joho, left, and Dung Le
This type of response was unheard of rapidly became the worldwide model for only be accomplished with additional
how to combat the disease. and keep the best and brightest young
before the GVAX vaccine. These results research.” clinicians and scientists,” says Jaffee. “WHEN I CAME TO THE KIMMEL CANCER CENTER, IT WAS CLEAR THAT
and news of promising research coming “The Skip Viragh Center and Viragh
Scholars program, established through Expanding Research “Our young scientists are essential to RESEARCH IS COMPLETELY DIRECTED AT HELPING THE PATIENT.
out of the Jaffee laboratory attracted continuing discovery.”
worldwide attention, and patients Skip’s profound generosity, have made the In 2016, another patient of Laheru’s THE PEOPLE CARE.THERE IS A SENSE OF HOPE. DR. LE SAW ME AS A
Kimmel Cancer Center a powerhouse in made a gift to advance pancreatic cancer Le, the first Viragh Scholar, played
called—more than 60 a month—for a leading role in identifying a genetic PERSON, NOT A DISEASE. BECAUSE OF THAT, I FEEL LIKE SHE SAVED MY
appointments at the Kimmel Cancer developing new treatments for pancreatic research. Linda Rubin, 65, lost her life to
cancer,” says Laheru. “We are able to the cancer this year, and like Viragh, she alteration known as mismatch repair LIFE BEFORE I EVER HAD MY FIRST IMMUNE THERAPY TREATMENT,”
Center. “There is no other cancer center as a critical biomarker for response to
doing this kind of work,” says Zheng. It recruit and retain the best pancreatic believed so strongly in the work of Laheru –STEFANIE JOHO
cancer scientists, realize revolutionary and Jaffee that she established the Linda an immune therapy, called checkpoint
earned the Kimmel Cancer Center the blockade.
reputation as the leader in pancreatic laboratory and clinical advances, and Rubin Fellowship in Pancreatic Cancer causes treatments to stop working, but it therapy with the checkpoint blockade
provide unparalleled care to patients.” Research and Patient Care. Immune checkpoints are one of
cancer research and treatment. “Everyone the main mechanisms cancer cells use seems to make immune therapies work nivolumab in patients with mismatch
attempted to do it, but the Kimmel The influx of patients that came from “As a former teacher and practicing better,” says Le. repair deficiency.
these discoveries and the creation of the veterinarian for 35 years, I have had the to suppress an immune response. The
Cancer Center was able to accomplish it large numbers of mutations common to Some of the early responses in a clinical Stefanie Joho, 25, was one of the
in a better way,” says Margaret Tempero, Skip Viragh Center transformed cancer opportunity to both learn from and teach trial of 48 patients were so dramatic that patients who participated in the clinical
care, creating a clinic model that brought and to mentor talented people. Education mismatch repair alterations serve as an
director of the University of California alert to immune cells because they make they were featured in the prestigious trial. She was near death, battling an
San Francisco Pancreas Cancer Program. together experts from every discipline is the future, and I want to be a part of that New England Journal of Medicine and at aggressive hereditary colon cancer that did
involved in treating pancreatic cancer. future in any way I can,” said Rubin. “The the tumor look very different from normal
Despite the accolades and reputation, cells. “For other treatments, including the 2015 and 2016 American Society of not respond to surgery or chemotherapy.
Jaffee and Laheru recognize there is much Experts from around the world and best we can hope for is that intelligence, Clinical Oncology meeting. They led to Out of options and in excruciating
the country come to the Kimmel Cancer novel thinking and focused determination chemotherapy, the changing tumor
more work to do. They are working to biology due to accumulating mutations FDA breakthrough status for immune pain, she searched desperately for other
improve immune therapies for pancreatic Center to learn what makes the Skip will lead the way out of the dark world of
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attract the attention of the cancer- continuing tightening of federal funding, discoveries at the Kimmel Cancer Center. percent of people survived past five years,”
killing immune T cells,” says Jaffee. it is becoming increasingly difficult for He decided to make an appointment at its says Ogle.
She is working with Lutz and others to those just starting out in their careers to Skip Viragh Center for Pancreas Cancer “Enrolling in the vaccine trial was an
convert the cancer to one that is immune compete for research funding,” Jaffee says. Clinical Research and Patient Care. easy decision for me,” says Ogle. “I still
responsive. It calls for using the vaccine “Private support has become essential to Despite the diagnosis, there was had no hope that I would survive, but I
to recruit T cells along with immune the progress of research.” some good news. His cancer was not thought if I participated in the vaccine
checkpoint blockades that are targeted The benefit of research is undeniable as as advanced as his father’s, and he was
specifically to the immune checkpoints new opportunities to improve pancreatic a candidate for a Whipple procedure,
in each patient’s cancer that could keep cancer treatment abound at the Kimmel a complex pancreatic cancer surgery
the T cells from going into action against Cancer Center. perfected at Johns Hopkins. At the
the cancer. The new approach looks appointment, research nurse Carol
promising in mouse models, and clinical Long-Lasting Responses Judkins also talked to him about a
trials in patients are in planning. Gene Ogle is an example of someone clinical trial testing the value of giving a
The group is also exploring the benefit whose cancer continues to respond to pancreatic cancer vaccine before surgery.
of giving the vaccine before surgery. immune therapy. He benefited from The pancreatic vaccine could
“Pancreatic cancer is notorious for being research that showed that giving the supercharge his immune system,
in areas outside of the pancreas, and the vaccine before surgery could help drawing cancer-attacking killer T cells
vaccine allows us to get ahead of the many patients. to pancreatic tumors. Jaffee and Laheru
Ana DeJesus-Acosta Nilo Azad
disease and get microscopic cancer cells When Ogle’s doctor told him he had had laboratory evidence that giving the
that surgery might miss,” says Laheru. pancreatic cancer, his first question was: vaccine before surgery gave the immune
treatments until she found Le, who Ana DeJesus-Acosta is another “How long do I have to live?” He was system a step up on the cancer and might
treated her with immune checkpoint Viragh Scholar working on new just 54 years old when he got the news, help it get at microscopic cancer cells that Gene Ogle
“PANCREATIC CANCER IS and his thoughts immediately turned to
blockade therapy. “At another cancer therapies for pancreatic cancer. She is could cause the cancer to spread. She was
center I went to, I felt like the doctors collaborating with basic scientists who NOTORIOUS FOR BEING IN AREAS his father, who died of the same disease working with Le and Zheng to explore
were more focused on how I could help are deciphering the molecular pathways 30 years earlier, at 63. Although many whether earlier use of the vaccine would “A LOT OF PROGRESS HAS BEEN
OUTSIDE OF THE PANCREAS, AND
them advance their research than on how pancreatic cancer uses to develop, years had passed, his memory was clear. provide a clinical advantage.
THE VACCINE ALLOWS US TO GET “My father died two months after he was MADE, BUT THERE IS STILL
they could help me survive my cancer. grow and spread to identify drugs that Ogle was well aware of the high rate of
When I came to the Kimmel Cancer target these mechanisms. One pathway, AHEAD OF THE DISEASE AND GET diagnosed. My knowledge was that it was pancreatic cancer spread and recurrence. A LONG WAY TO GO. THAT’S
Center, it was so different. It is clear that known as Hedgehog, was discovered at incurable and killed quickly.” As an engineer, he is a numbers guy. He
MICROSCOPIC CANCER CELLS THE ONLY WAY WE’RE GOING
research is completely directed at helping Johns Hopkins and linked to pancreatic Ogle’s doctor told him that there had recalled a survival chart he saw around the
the patient. The people care. There is a cancer development. DeJesus-Acosta is THAT SURGERY MIGHT MISS.” been many advances since his father’s TO PERMANENTLY MOVE THAT
time of his surgery. “It peaked at one year
sense of hope. Dr. Le saw me as a person, collaborating with other investigators to –DANIEL LAHERU diagnosis and specifically referred to and went down after that. Less than 5 SURVIVAL CURVE.” –GENE OGLE
not a disease. Because of that, I feel like determine if targeting Hedgehog could
she saved my life before I ever had my first combat pancreatic cancer. She is currently Other variations include combined
immune therapy treatment,” says Joho. As conducting clinical studies of Hedgehog treatments. In some patients, giving
of her last appointment, Joho says, there is pathway inhibitors in combination with the immune-modulating drug
no evidence of cancer. “I haven’t felt this chemotherapy and radiation therapy to cyclophosphamide before the vaccine WHEN JOSEPH EDENS began experiencing
well in a long time,” she says. see if it can knock back the cancer to get causes immune structures to form inside abdominal pain, he knew something wasn’t right, but he
“It is rare to get a response in colon more patients to surgery. WATCH HIS STORY:
tumors that help regulate immune cell didn’t expect to learn he had pancreatic cancer. “The
cancer patients who have not responded Nilo Azad received Viragh funding http://bit.ly/PancreaticPatients
activation. “These organized immune
to other standard therapies, and most of to test the benefit of epigenetic therapy structures do not naturally appear in worst thing I could have thought of happened,” he says
them had just months to live,” says Le. in pancreatic cancer patients treated pancreatic cancers,” says Zheng. “This of the diagnosis. His mind immediately went to his wife
She is hopeful this discovery will benefit with surgery. Laboratory research in suggests that there has been significant and two children. He did his research. He knew the
many more patients. She is planning colon cancer and clinical studies in lung reprogramming of immune cells within survival statistics, but he was determined to beat the
larger clinical studies in many cancers, cancer suggest that epigenetic therapies— the tumor.” There is evidence that adding
including pancreatic cancer. treatments that target chemical alterations cancer. “We looked nationwide and worldwide for the
a checkpoint blockade treatment to the
to DNA that change the behavior of mix could further enhance immune best place for pancreatic cancer, and that turned out to
cells—may make cancers more vulnerable activity. be Johns Hopkins,” he says. Edens’ cancer was treated by
to a commonly used class of drugs called Another combined approach adds surgeon Christopher Wolfgang and medical oncologist
taxanes. a second kind of vaccine, a weakened Lei Zheng, but many specialists collaborated to prevent
Viragh Scholar Zheng is collaborating version of the bacterium Listeria. The
with Laheru, Le, Lutz and Jaffee to the cancer from recurring and to manage the digestive
Listeria is genetically modified to be safe
optimize the effects of the pioneering for humans but stimulates an immune changes that result when the pancreas is removed. “This
GVAX vaccine. They are making tweaks response against the protein mesothelin. is an example of the multispecialty care provided at the
in timing of vaccination and changes to its Jaffee and Le believe the protein helps Kimmel Cancer Center. Experts in surgery, oncology,
composition and delivery that they hope pancreatic cancer cells to grow and spread.
will boost its cancer-killing capabilities, gastroenterology and endocrinology all participated in
“The combination essentially trains the
and make the vaccine a treatment option body to recognize and attack pancreatic Mr. Edens’ care,” says Zheng. Six years later, he remains
for many more patients. tumors,” says Le. cancer-free.
“Pancreatic cancer tends to have a “The contribution of our young
low number of mutations that do not investigators is clear, but with the
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study, I might be able to help doctors move
that survival curve far beyond 5 percent.”
That was nearly six years go, and
contrary to the statistics and his own Jaffee Appointed to National Cancer Stand Up To Cancer
personal predictions, Ogle is alive and Leadership Initiatives Elizabeth Jaffee is a team leader of the Stand Up To Cancer-
doing well. It’s been almost four years The Lustgarten Foundation Pancreatic Cancer Convergence
since his final vaccination. His cancer isn’t Dream Team charged with bringing all specialties together to
gone, but it’s not growing. With the boost fight pancreatic cancer.
from the vaccine, his immune system
appears to be keeping it in check. “I’m “We are focusing on how the immune system shapes cancer
still here, and I want to be a message of and how we can alter the immune system to fight it,” says
hope to others,” he says. Jaffee. “We believe the immune system has the power to
Ogle fully expected to become a ultimately defeat pancreatic cancer.”
pancreatic statistic, but not a positive Jaffee, an international leader in cancer immunology, has
one. “My perspective is changing,” he focused her career on understanding the biology of pancreatic
says. He is certain the wonderful care he cancer and how to use the immune system against it. “I
received, including surgery, chemotherapy, believe we are on the verge of many good therapies that are
radiation therapy and particularly the Elizabeth Jaffee, co-chair of the Cancer Moonshot Blue Ribbon not toxic and give patients a good quality of life,” says Jaffee,
pancreatic cancer vaccine, allowed him to Panel, speaks at a White House press briefing. Jaffee is deputy an associate director of the Bloomberg~Kimmel Institute
beat the odds. “I’m so proud to be a part director of the Kimmel Cancer Center, co-director of the Skip for Cancer Immunotherapy. “This is a new era for using the
of these studies. It’s a huge honor,” says Viragh Center for Pancreas Cancer Clinical Research and immune system to fight cancer.”
Ogle. “Everyone who took care of me— Patient Care, and associate director of the Bloomberg~Kimmel
from the receptionist to the nurses and Institute for Cancer Immunotherapy
doctors—was top-notch. They all had so
much compassion.” “The science is here.The time is right. Our
Over the last six years, Ogle estimates that field is energized. We hope this will
he’s made the 270-mile trip from his home
in Roanoke, Virginia, to the Skip Viragh turn into therapies that can potentially cure
Center at least 100 times. There were other patients with metastatic disease. I truthfully
comprehensive cancer centers and some
ood community hospitals much closer to
believe it will lead to better outcomes.”
his home. In fact, many of his relatives and
friends questioned his choice to travel so far.
“I did my research before I made a decision, Cancer Moonshot Initiative
and Johns Hopkins came up on top,” says The 21st Century Cures Act received nearly unanimous
Ogle. “I have never regretted that decision— approval by the U.S. Senate. The bill includes $4.8 billion
not one time.” in new funding for the National Institutes of Health,
Ogle recently celebrated his 60th including $1.8 billion for the National Cancer Moonshot
birthday, a milestone he never expected to initiative, championed by Vice President Joe Biden and
Elizabeth Jaffee reach. He is also spending time with his aimed at solving cancer’s greatest challenges. Elizabeth
three grandchildren, two of whom were Jaffee was selected as co-chair of the Cancer Moonshot Blue
born after his diagnosis. “I am so thankful Ribbon Panel and also serves as co-chair of the initiative’s
“THIS IS THE TYPE OF PROGRESS I IMAGINED THREE DECADES AGO,WHEN I that I lived to see them. I didn’t think I Immunology Working Group.
FIRST BEGAN STUDYING THE IMMUNE SYSTEM. FOR THE FIRST TIME, I THINK would,” he says. “I’m beating this disease.
THE POSSIBILITIES ARE REALLY LIMITLESS.” That’s a message people need to hear.” Jaffee is charged with helping to set the direction for the
He wants everyone to understand the Cancer Moonshot and recently announced recommendations The Kimmel Cancer Center’s Stephen Baylin, Elizabeth Jaffe
–ELIZABETH JAFFEE power and the value of research. “A lot of and William Nelson participated in the 2016 Stand Up To
at a White House press briefing for speeding the pace of
progress has been made, but there is still a cancer discovery. Cancer Telethon held last September.
long way to go,” he says. “That’s the only
The Pancreatic Cancer Multidisciplinary Clinic is a one-day clinic that way we’re going to permanently move that
offers a complete, comprehensive examination, including imaging tests, such as CT survival curve.”
scans, by some of the top cancer experts in the country. To make an appointment, Jaffee agrees. She says: “This is the type 10 Years of Progress in 5
call 410-933-PANC(7262).
of progress I imagined three decades ago, Blue Ribbon Panel Recommendations
when I first began studying the immune • Establish a network for direct patient involvement in cancer • Intensify research on the major drivers of childhood cancers.
system. For the first time, I think the research. • Minimize cancer treatment’s debilitating side effects.
PancMD Video Series The PancMD video series introduces you to the Johns
possibilities are really limitless.” n • Create a translational science network devoted exclusively to • Expand use of proven prevention and early detection strategies.
Hopkins experts who gather their knowledge and expertise for patients in the
Pancreatic Cancer Multidisciplinary Clinic, including Daniel Laheru and Barbara immunotherapy. • Mine past patient data to predict future patient outcomes.
Biedrzycki. Topics include medical oncology, nutrition, radiology, surgery, genetics, • Develop ways to overcome resistance to therapy. • Develop a 3-D cancer atlas.
• Build a national cancer data ecosystem. • Develop new cancer technologies.
and clinical trials. Watch the videos at: http://bit.ly/pancvideos.
Read the Blue Ribbon Panel Report at cancer.gov/brp. Watch a video: youtu.be/uQBNApEb1a8
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25 Years of Cancer
Immunology Discovery NEWSFOCUS
1989
Cancer immunology researchers Elizabeth Jaffee, Drew Pardoll and
2013
Science magazine calls cancer immunotherapy the Breakthrough of Cancer Immunotherapy
Hyam Levitsky develop GVAX, the first therapeutic cancer vaccine.
Downloaded from www.sciencemag.org on April 12, 2014
This year marks a turning point in cancer, as long-sought efforts to unleash the immune
the Year and cites work by Kimmel Cancer Center scientists. system against tumors are paying off—even if the future remains a question mark
This work led to the development of pancreatic, prostate, kidney, History’s path is unchartable when it’s not yet past a grounded-in-reality bunch, say a corner has been turned
but present, when we are still standing in the mid- and we won’t be going back.
breast and other cancer vaccines.
dle of it. That’s what made Science’s selection of this With much pressure these days to transform biological
2014
year’s Breakthrough of the Year such a topic of inter- insights into lifesaving drugs, there’s a lesson to be learned
nal debate, even anxiety. In celebrating cancer immu- from immunotherapy’s successes: They emerged from a
notherapy—harnessing the immune system to battle careful decoding of basic biology that spanned many
tumors—did we risk hyping an approach whose ultimate years. The early steps were taken by cancer immunologist
impact remains unknown? Were we irresponsible to label James Allison, now at the University of Texas MD
as a breakthrough a strategy that has touched a tiny fraction Anderson Cancer Center in Houston. In the late 1980s,
of cancer patients and helped only some of them? What do French researchers who weren’t thinking about cancer
2000 Jaffee, Lei Zheng, Eric Lutz, Laheru and their Skip Viragh Center team
we mean when we call something a breakthrough, anyway? at all identified a new protein receptor on the surface of
Ultimately, we concluded, cancer immunotherapy T cells, called cytotoxic T-lymphocyte antigen 4, or
passes the test. It does so because this year, clinical trials CTLA-4. Allison found that CTLA-4 puts the brakes
have cemented its potential in patients and swayed even on T cells, preventing them from
the skeptics. The field hums with stories of lives extended: launching full-out immune attacks.
Online
developed and tested a vaccine that triggered the growth of immune
the woman with a grapefruit-size tumor in her lung from He wondered whether blocking the
melanoma, alive and healthy 13 years later; the 6-year- blocker—the CTLA-4 molecule— sciencemag.org
Scientists discover the immune system-related molecules PD-L1 and
old near death from leukemia, now in third grade and in would set the immune system free to Podcasts,
videos, and other
remission; the man with metastatic kidney cancer whose destroy cancer. extras (http://scim.ag/
disease continued fading away even after treatment stopped. Allison’s rationale was untested. med_6165).
cell nodules within pancreatic tumors, essentially reprogramming
As the anecdotes coalesce into data, there’s He and his colleagues changed
another layer, too, a sense of paradigms shifting. the conversation, in the words of one cancer researcher,
PD-L2 on the surface of cancer cells. Known as immune checkpoints,
Immunotherapy marks an entirely different “to consider immunosuppression as the focal point, and
way of treating cancer—by targeting manipulation of immunosuppression as the target.”
the immune system, not the Doing so took time. CTLA-4 was discovered in 1987.
these intractable cancers and potentially making them vulnerable to
tumor itself. Oncologists, In 1996, Allison published a paper in Science showing
that antibodies against CTLA-4 erased tumors in mice.
they are found to partner with PD-1 to hide cancer cells from the Seek and destroy. Instead of targeting tumors directly, cancer
immunotherapy enlists the immune system to attack them. Here,
immune-based therapies.
an antibody (pink) blocks a receptor (purple) found on T cells
(gray), setting off a chain reaction that leads to an assault on
immune system.
cancer cells (brown).
Researchers test a combination of the GVAX
2001
1432 20 DECEMBER 2013 VOL 342 SCIENCE www.sciencemag.org
Published by AAAS
vaccine with a second one that contains a
Jaffee, Daniel Laheru and team conducted the first clinical studies of a modified version of the bacterium Listeria in
pioneering therapeutic pancreatic cancer vaccine. 90 pancreatic cancer patients.
2005 2015
Early results of GVAX are encouraging; it becomes one of the few Viragh Scholar Dung Le leads a study of mistakes in so-called
new therapies to increase survival in some patients with pancreatic mismatch repair genes that accurately predict who will respond to
cancer. certain immunotherapy drugs known as PD-1 inhibitors.
2007 2016
Clinical trials of experimental drugs that target and interfere with the Mismatch repair biomarker receives FDA breakthrough status.
PD-1 molecule begin.
With leading funding from Michael
2009 Bloomberg and Sidney Kimmel,
the Bloomberg~Kimmel Institute
The Skip Viragh Center for Pancreas Cancer Clinical Research and
for Cancer Immunotherapy is announced at Johns Hopkins. Vice
Patient Care opens, accelerating pancreatic cancer immune therapy
President Joe Biden calls it a model for driving progress and the site
advances.
of some of the next generation’s breakthroughs in cancer treatments.
2010 Jaffee is named co-chair of the Vice President’s Cancer Moonshot
Johns Hopkins Kimmel Cancer Center scientists lead an early clinical Blue Ribbon Panel and chair of the National Cancer Advisory Board.
trial of the experimental checkpoint blockade-targeting drug MDX-
1106, now known as Bristol-Myers Squibb’s nivolumab (Opdivo).
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The Next Generation of in combination with other therapies the immune system, Lee says. As cancer
Pancreatic Cancer Pioneers would potentially improve anticancer
immunity, he says.
He is confident that Kimmel Cancer
Center immunology experts can decipher
cells die, they release their proteins into
the body. Essentially, they show their
true colors to the immune system, which
now recognizes them as abnormal cells;
The Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care attracts the the complexity of the immune response. immune cells are then deployed to the
most accomplished young investigators interested in pursuing a career in pancreatic cancer He argues that cancer isn’t as smart as it tumor. Patients will then, hopefully, get
is often portrayed. It doesn’t intelligently surgery and chemotherapy, followed by
research and treatment. By training with established investigators, Skip Viragh Center fellows select these regulatory processes to save more immunotherapy, with the goal of
are helping advance the science and bringing much-needed new therapies to patients. itself; it just gets lucky, he says. He likens keeping the tumors at bay.
the cancer cell to a person working at With funding support from the United
a computer. “Rather than intelligently Company Charitable Foundation and the
in T cells that will be specifically targeted typing words into a computer, the cancer James W. and Frances Gibson McGlothlin
to pancreatic cancer cells. “WE GET CURES BECAUSE WE ARE cell just presses a bunch of buttons on the Foundation of Bristol, Va, the Kimmel
keyboard until it finds one that works, Valerie Lee Cancer Center will soon begin a clinical
Immune therapy offers one of the SMARTER THAN THE CANCER.
only promising treatments for the most and it keeps pushing it until it doesn’t trial in 54 patients to study the combined
WE JUST NEED TO KNOW WHAT work anymore,” says Johnson. “Cancer Zheng and Ella-Mae Shupe, Lee’s focus therapy. Lee wants to see if it works well
advanced pancreatic cancers that cannot
be controlled with surgery, chemotherapy TO TARGET.” –RUSTY JOHNSON hasn’t outsmarted us. If it had, it would is on locally advanced pancreatic cancer. enough against the cancer to get more
or radiation therapy. kill every time. It doesn’t. We get cures Although the cancer has not invaded patients to surgery, where their cancers
immune response and prevent immune because we are smarter than the cancer. other organs (metastatic), it has begun could be cured. At a minimum, she
cells from attacking normal cells, but We just need to know what to target.” to attach itself to the tissue and vessels hopes it will keep patients’ cancers from
cancer cells co-opt it to hide from the That’s precisely what he is hoping to around the pancreas and, as a result, it spreading- and potentially keep them in
immune system. Clinical trials of drugs accomplish in the Jaffee lab, which he cannot be treated with surgery. About 40 check for a long time.
that block IDO appear to make other sought out specifically for its pioneering percent of patients diagnosed have this Lee completed her fellowship in June
immune therapies work better. role in advancing cancer immunology form of the cancer. “Right now, we don’t 2016 and is helping expand pancreatic
Johnson believes there are many other research and its translation to patients. have many treatment options for them,” cancer clinical trials to the national capital
Katherine Bever cells and pathways that play a role in “The Kimmel Cancer Center is says Lee. They receive the same treatment region at Johns Hopkins’ Sibley Memorial
immune suppression. “Figuring out the tremendously unique,” says Johnson. that patients with metastatic pancreatic Hospital in Washington, D.C.
Hope For the Most Advanced mechanism behind how those cells work “It is the worldwide epicenter of cancer get, she says.
Pancreatic Cancers is critical to discovering new targets to pancreatic cancer and cancer immunology Lee’s approach could make curative
translational research because of Liz and surgery an option for many more No Pain, Significant Gain
Katherine Bever is collaborating with stimulate antitumor immunity,” he says. Pancreatic cancers have a knack for
Dung Le to bring hope to patients facing Some, like IDO, may work through Dan.” patients. It combines anticancer drugs,
Johnson says he came from an a pancreatic cancer vaccine, an exciting hijacking the functions of cells around
the worst form of pancreatic cancer. Bever checkpoints to regulate the immune the tumor to create a cancer-friendly
and Le are developing clinical trials for system, but others may have another institution that did not embrace new type of immune therapy known as an
collaboration or have the strong donor immune checkpoint blockade and a very environment. Blocking these changes
patients with advanced pancreatic cancers Rusty Johnson primary mechanism of action. “What they has been a focus for Zheng, an
that have spread outside of the pancreas. do and how they do it is currently a black involvement so common at the Kimmel precise form of radiation therapy called
Cancer Center. He says the intense and stereotactic body radiation therapy. investigator in Jaffee’s laboratory.
One immune therapy trial combines the box,” says Johnson. Adrian Murphy has zeroed in
pancreatic cancer vaccine GVAX to bring Rare Findings Could Help Many He is particularly interested in unique collaboration between scientists The therapy uses standard anticancer
and clinicians at the Kimmel Cancer drugs to stabilize the cancer, followed by on one of the changes identified by
cancer-killing T cells to pancreatic tumors Rusty Johnson would like to better improving the activity of the pancreatic Zheng. Targeting it, he believes, could
with immune checkpoint inhibitors to understand rare immune cells involved in cancer vaccine developed and moved Center’s Skip Viragh Center is remarkably the Jaffee-developed pancreatic cancer
efficient at studying immunotherapy vaccine. The vaccine awakens the immune simultaneously fight the cancer and
block PD-1 and IDO, that in many regulating the immune system’s response to the clinic by his mentors, Elizabeth combat a common and painful side effect.
cancers act like an off-switch for T cells to cancer. These are cells that are so poorly Jaffee and Daniel Laheru. Vaccines treatments and getting them into system, summoning cancer-fighting killer
clinical trials. “It is amazing to be at a T cells to the tumor. Treatment with Zheng’s research revealed Sema3D as a
and shut down the immune response. understood that they have not been accelerate the immune response, bringing neural highway of sorts, allowing cancer cells
They plan to treat patients with PD-1 written about in most medical textbooks. in many powerful cancer-killing T cells, center where you can study what you a new checkpoint blockade immune
think is going to help others and have therapy known as anti-PD-1 disrupts a to hitchhike on nerve cells to travel away
and IDO inhibitors and the GVAX vaccine Johnson believes a better understanding only to be held at bay by checkpoint from the main tumor. This painful invasion
followed by the listeria vaccine. Listeria of these cells may lead to new, targeted inhibitors, like IDO, PD-1, CTLA-4, donors generously step up to provide the mechanism cancer cells use to hide from
funding,” says Johnson. these T cells. Lee hopes that together, of nerve cells is also deadly because it is a
bacteria augment the vaccine response and treatments that could improve the LAG3 and others, which put the brakes mechanism the cancer uses to spread—a
are engineered to express mesothelin, an effectiveness of existing immune therapies. on the immune response. “I believe there these therapies will cause the patient’s
own immune system to attack the mechanism, Murphy says, that is currently
immune cell-alerting antigen or tumor He was inspired by his earlier research are cells that can be both accelerators and Combining for a Cure untargeted in pancreatic cancer therapy.
characteristic common to many pancreatic of the IDO pathway, a mechanism tumors brakes, depending upon their cellular cancer. Patients receive two doses of this
Valerie Lee is investigating a new treat- combined regimen three weeks apart. He hopes to change that and is
cancers. Bever hopes the combined use to suppress the immune system and environment. We need to harness that ment approach that may make currently working with Jaffee and Zheng to develop
approach will synergistically remove the one that has been associated with poor power and use it against cancer,” says Next, patients begin five days of
incurable pancreatic cancers curable. radiation therapy. This treatment destroys therapies that could block Sema3D. “If
breaks from the immune system and bring outcomes in many types of cancer. IDO’s Johnson. Targeting these cells with drugs Working with Jaffee, Laheru, Lei we develop drugs that inhibit this process,
normal function is to help regulate the pancreatic cancer cells and also awakens
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GVAX, anti-PD-1 immune checkpoint of immune cells that are able to enter to different types of immune therapies.
blockade and a macrophage-modulating the tumor and improve the response to She expects this research to reveal new
agent in an effort to release the biological immune therapy,” says Roussos Torres. immune targets for therapy and biomarkers
brakes the cancer cells places on the Her research has a basic science that predict whether a cancer will or will
immune system. component aimed at studying the various not respond to immune therapy.
Patients who have pancreatic cancers immune therapies and their effects on Thompson will compare tumor
that currently cannot be successfully the tumor and tumor microenvironment. biopsies obtained before treatment to
removed with surgery would first receive From that, she hopes to develop a samples taken at surgery. For pancreatic
chemotherapy and radiation treatment “readout of responses” that will provide cancers that cannot be treated with
followed by two rounds of treatment with clues about why certain immune therapies surgery, she will use biopsies taken
immune therapy. Saung and Zheng hope work or do not work. Understanding at different time points throughout
the novel treatment approach will improve what occurs at the molecular level may diagnosis and treatment. Thompson
upon our current ability to knock back reveal important biomarkers that can will use advanced technologies, such as
the tumor enough for surgical removal. guide therapy. flow cytometry and DNA sequencing,
Adrian Murphy Immune therapy continues after surgery Evanthia Roussos Torres On the clinical side, Jaffee and to sort through and collect immune cells Mark Yarchoan
to keep immune cells ignited against the Roussos Torres are collaborating with for study and to identify proteins that
it could reduce nerve pain and also work cancer and to clean up any microscopic their breast cancer colleagues Vered influence immune activity. In addition, identified, including IDO, LAG3 and
on the cancer,” says Murphy. cancer cells that escape surgery. “BREAST CANCER TRADITIONALLY Stearns and Roisin Connolly, who are a sophisticated technology known as CD40, that can be targeted with other
Pain is a common side effect for IS NOT THOUGHT OF AS HIGHLY helping them collect tissue samples from multiplex immunohistochemistry will be inhibitors. Yarchoan believes adding a
pancreatic cancer patients. Murphy says patients receiving epigenetic therapy in used to visualize the spatial composition checkpoint inhibitor to vaccine therapy
that many of the drugs used to treat nerve IMMUNOGENIC.THE SAME IS TRUE
conjunction with an immune therapy of immune cells within tumors. might improve responses in pancreatic
pain do not work well and have their own OF PANCREATIC CANCER, SO I known as a PD-1 immune checkpoint “Cancers tend to change, mutating cancer as adding ipilumumab to
toxicities. What’s more, none of these THOUGHT INVESTIGATING inhibitor. “We know that there is their DNA to survive in the face of nivolumab did in melanoma.
therapies combat the root cause of the potential for epigenetic therapies to make different treatments,” says Thompson. PD-1 checkpoint inhibitor therapy
pain—the cancer. Murphy’s approach BREAST CANCER THE WAY PD-1 immune therapy work better, but “This work will help us better understand has been a major breakthrough at the
shows promise for accomplishing both by WE RESEARCH PANCREATIC we don’t fully understand how or why and target these changes to keep the Kimmel Cancer Center, resulting in
preventing the cancer from spreading to it works. That’s what we’re hoping to immune system active as the tumor remarkable responses in melanoma and
nerve cells. CANCER MIGHT PROVIDE LEADS.”
uncover,” says Roussos Torres. evolves.” lung cancer, and showing the potential
–EVANTHIA ROUSSOS TORRES
He is currently scanning a library Initially, she will focus on triple-negative Her ultimate goal is to convert even to have benefit across essentially all
of FDA-approved drugs for potential breast cancer because of the great need for the most advanced pancreatic cancers to a cancer types. “The research is so new
Sema3D targets. Murphy will test drugs Pancreatic Cancer and Beyond more effective therapies, but she believes chronic, manageable disease. that no one knows what to mix the
using a pancreatic cell line developed Advances made in Jaffee’s laboratory have what they learn could possibly be applied PD-1 inhibitors with at this point for
specifically to screen candidate drugs. focused on pancreatic cancer, but what to other types of breast cancer as well. pancreatic cancer,” says Yarchoan. “I want
“Laboratory research shows that May Tun Saung she and her team of investigators and Combinations That Make Vaccine to learn how we can add in other immune
Sema3D is involved in pancreatic cancer clinicians have learned about immune Therapy Work Better checkpoint inhibitors to take advantage
metastasis,” says Murphy. “Using a drug Saung is forming collaborations therapy is being applied to other cancers. Mark Yarchoan, the Linda Rubin Fellow, of the incredible T cell activation the
to block it could benefit both the spread with Justin Hanes, Director of the This is the case for Evanthia Roussos is hoping to build upon Jaffee’s work vaccine gives us.” The first step of his
of cancer and the associated pain.” Center for Nanomedicine, and Hai- Torres, who is working in the Jaffee lab on the pancreatic cancer vaccine. He is research will focus on defining the best
Quan Mao, Associate Director of the with the hope of translating some of their studying whether combining additional checkpoint inhibitors—or combinations
Institute for NanoBioTechnology, to immunology discoveries to breast cancer. immune therapies with the vaccine makes of inhibitors—to add with the vaccine.
Immune Therapy Combo and “Breast cancer traditionally is not
Nanomedicine develop nanoparticles that enhance the killer T cells the vaccine recruits to “The vaccine is the first step in turning
tumor immunity. Nanoparticles are tiny thought of as highly immunogenic. The tumors better at destroying cancer cells. pancreatic cancer into an immune-
May Tun Saung is working with same is true of pancreatic cancer, so I
pancreatic cancer expert Lei Zheng to nano-scale structures that are larger than Before Jaffee and team’s pancreatic responsive cancer. Now that the vaccine
molecules. In cancer medicine, they can thought investigating breast cancer the cancer vaccine, cancer-fighting immune has gotten T cells into the cancer, we need
develop combination immunotherapies way we research pancreatic cancer might
to improve the effectiveness of treatments. be used to improve the effectiveness and cells were not usually found in pancreatic to let them do their work by removing as
efficiency of transporting drugs to tumors. provide leads,” says Roussos Torres. tumors, says Yarchoan. “I’m hoping we many blocks against the immune system
Saung is focusing on a particular type of Using techniques fashioned in the Jaffee
immune cell called a macrophage. It is a Saung envisions nanoparticles loaded can push immune therapy even further as we can,” says Yarchoan.
with tumor antigens to stir an immune lab, Roussos Torres is exploring alterations by adding in additional immunotherapies Although still in a very early stage, he
large white blood cell that plays a critical in immune cells in and around the tumor
role in the body’s immune response but response specifically against the cancer and Liz Thompson that make T cells work better within the is also investigating opportunities to apply
immune therapy molecules on the surfaces that may be influencing the behavior cancer,” he says. precision, or personalized, medicine to
is corrupted by cancer, switching roles of the cancer. “We want to teach the
to aid the tumor instead of destroying to keep the immune response active. “In melanoma, patients are more immune therapy. Yarchoan will explore
Precision medicine approaches are possible microenvironment in the tumor to be more Using Pathology to Improve likely to respond to a combination of whether the mechanism that prevents T
it. “Our goal is to convert macrophages immunogenic and help the cancer respond Immune Therapies
from immune suppressing to immune as patients’ tumors could be sequenced to ipilumumab and nivolumab than if cells from doing their job may vary among
identify the specific molecules that may better to immune therapies,” she says. Liz Thompson is a new faculty member,
activating,” says Saung. either agent is used alone,” says Yarchoan. patients. “Potentially, we could customize
provoke improved immune signals against Epigenetics is the study of alterations collaborating with Skip Viragh Center The drugs are known as a checkpoint
In the laboratory, she is working what we combine the vaccine with at an
the cancer cells. Nanoparticles could to the chemical environment of DNA co-directors Elizabeth Jaffee and Daniel inhibitors for their ability to shut
with Zheng to explore drugs that target individual level,” he says. His ultimate
include these molecules to generate an that can change gene function. There is Laheru, clinician-scientist Lei Zheng and
macrophages, in combination with GVAX down a mechanism that cancer cells goal is to broaden and improve response
anti-tumor response specific to a patient’s, evidence that epigenetic-targeted drugs pathologist Ralph Hruban. As a surgical use to suppress an immune response.
and anti-PD-1 checkpoint inhibitors, to rates to the pancreatic cancer vaccine. n
unleashing a more potent immune can prime the immune system to mount pathologist, she is focused on deciphering Ipilimumab targets the CTLA-4 immune
enhance the anti-tumor immune response. a better response against cancer. “We and characterizing the immune response at
She is developing a clinical trial that response against the cancer. checkpoint, and nivolumab targets the
are hoping to use epigenetics to turn on all stages of pancreatic cancer, particularly PD-1 checkpoint, but there are many
combines the pancreatic cancer vaccine, gene expression that changes the types how immune activity changes in response others checkpoints that have been
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IN THE NEWS PHILANTHROPY
Molecular Conspiracy
A new genetic clue provides insight about
Zheng is collaborating with pancreatic
cancer expert Elizabeth Jaffee on
Swim Across America Supports Immune Therapy
how pancreatic cancer spreads. Three therapies that interfere with the proteins. More than $450,000 was raised at the 2016
proteins, annexin A2, Sema3D and another “We are planning clinical trials with
a recently developed vaccine to target annual Swim Across America event. A portion
molecule, conspire to create the lethal
annexin A2,” says Zheng. “At the same of the proceeds will provide continued funding
characteristics that define pancreatic cancer.
Annexin A2 had previously been linked to time, we are developing a therapeutic for a Johns Hopkins-initiated breakthrough
poor survival rates, and this new finding by antibody targeting annexin A2, and we are immunotherapy clinical trial. Dung Le and
pancreatic cancer expert Lei Zheng reveals looking for another to target Sema3D.”
collaborators found that cancer cells deficient
more information about how it works with The researchers are still working to
decipher the molecular mechanisms at in repairing mismatched DNA sequences
the other two proteins to promote the
spread of pancreatic cancer. play but believe annexin A2 may work are most susceptible to treatment with a
as a bodyguard of sorts for Sema3D, checkpoint blockade immune therapy, called
sheltering and guiding the protein as it anti-PD1. The predictive test is the first
makes it way toward an exit at the cell
surface. It could also act like a professional biomarker across tumor types for anti-PD1
packer, helping enclose Sema3D in tiny immune therapy, warranting publication in the
Alison Klein
molecular bubbles that are secreted by prestigious New England Journal of Medicine.
cells, says Zheng. Once out of the cell, This had led the FDA to grant priority review
Sema3D works as a neural highway, and studying these changes can lead to a for a new indication for the PD-1 inhibitor. In
allowing cancer cells to hitchhike on nerve better understanding of why some people
cells to travel away from the main tumor. develop pancreatic cancer. If we combine 2015, when Swim Across America first began
The findings align with other pancreatic this information with data on other supporting the clinical trial, Forbes called it “the
cancer observations by Zheng and team. pancreatic cancer risk factors, we may be most exciting finding announced” when it was
“Pancreatic cancers are what we call able to identify and one day screen high- featured at the annual meeting of the American
neurotropic, meaning they tend to invade risk groups.”
Society of Clinical Oncology. Swim Across
nerves,” says Zheng. Earlier pancreatic Klein and collaborators have already
cancer vaccine research by Zheng found begun further studies of the gene regions America is an annual grass-roots event that
that long-term survivors who had been and have learned that several appear related began in 2010 and brings swimmers of all levels
treated with the vaccine had antibodies to DNA repair, cell growth and tumor together to raise money for cancer research
Lei Zheng
against annexin A2 in their tumors. suppression. They used genetic informa- through a pool and open-water swimming
The research was funded by the National tion from nearly 10,000 pancreatic cancer
“WE ARE PLANNING CLINICAL patients and more than 11,000 healthy event. The Baltimore event supports the Swim
Cancer Institute (RO1 CA169702, K23 Stefanie Joho, left, and Dung Le
TRIALS WITH A RECENTLY people collected during a four-year, inter- Across America Laboratory at the Kimmel
CA148964-01, HL42093, MOD FY15-226,
P50 CA062924, P30 CA006973), the national collaboration. “We knew there Cancer Center. n
DEVELOPED VACCINE TO TARGET were genetic variants to be found, and the
Viragh Foundation, the Skip Viragh Center
ANNEXIN A2,” SAYS ZHENG. for Pancreas Cancer Clinical Research large number of pancreatic cancers in this In 2015, when Swim Across America first began supporting the clinical trial, Forbes called it “the
“AT THE SAME TIME,WE ARE and Patient Care, the Lefkofsky Family analysis gave our study the power to find most exciting finding announced” when it was featured at the annual meeting of the American
Foundation, and the Lustgarten Foundation. more novel genes,” says Klein.
DEVELOPING A THERAPEUTIC The team hopes to further increase the Society of Clinical Oncology.
ANTIBODY TARGETING ANNEXIN number of cancers studied to obtain even
A2, AND WE ARE LOOKING FOR
Genetic Risks greater insight into the genetic variants
ANOTHER TO TARGET SEMA3D.”
In the largest study of its kind, researchers
have connected alterations in for
associated with pancreatic cancer, one
of the most lethal types of cancer. “We Gift Supports New Drug Combo Approach
regions of the genome that increase the know from our analysis that there are lots
–LEI ZHENG Anne Wyman, the Frederick W. Richmond Foundation, her daughter Elizabeth
risk of developing pancreatic cancer. of other variants we need to find to fully
Individually, these gene variations increase understand pancreatic cancer,” says Klein. McCance and the McCance Foundation Trust made a generous donation to help
In animal studies, annexin A2-free
mice never developed metastatic tumors, pancreatic cancer risk from 12 percent to The study also confirmed connections Dung Le continue a study of a combined five-drug approach for pancreatic cancer
but those that produced annexin A2 as much as 38 percent. between pancreatic cancer risk and several called GTX-CI. It uses the drugs gemcitabine, docetaxel, capecitabine, cisplatin
almost always did, getting tumors in “The variants are common in the genetic variants linked to other cancers. and irinotecan. This current study builds on a prior successful study with GTX-C
their liver, lungs and abdominal cavity. population, and most individuals who The research was supported by the initiated with funds from several donors, including Swim Across America and the Sol
In human tissue studies, Zheng and have them will never develop pancreatic National Institutes of Health (RO1
cancer,” says Alison Klein, a Sol Goldman Pancreatic Cancer Research Center. Le is studying lower, less toxic doses
collaborators observed a similar link CA154823).
between the proteins and pancreatic Goldman Pancreatic Cancer Research of the drugs as a way to attack pancreatic cancer at different points but also reduce
cancer recurrence and progression. Center researcher. “However, identifying treatment side effects. Elizabeth McCance, left, and Anne Wyman
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