Pancreatic Cancer Collective

The Collective awards its first $7 million in New Therapies Challenge Grants

The Pancreatic Cancer Collective, our strategic partnership with Stand Up To Cancer, has awarded a total of $7 million in first-round New Therapies Challenge grants to seven teams of top cancer researchers to explore new pancreatic cancer treatments. Each team will receive up to $1 million in initial funding, with $4 million per team for clinical studies awaiting the most successful projects in the second round. This, new two-tiered funding model is intended to increase the number of “shots on goal,” allowing rapid exploration of a relatively large number of promising ideas through $1 million, 14-months grants. The second round will support only the most promising projects with an additional $4 million over three years (subject to the specific needs of the project).

In addition to this new funding model, these grants have attracted several new researchers to the field from across the country. These teams are the first projects funded under the Pancreatic Cancer Collective launched last spring. The selection process was quite rigorous – out of 53 proposals, 10 were selected for in-person presentations and ultimately, seven were selected.

The overall goal of the New Therapies Challenge is to bring new, cutting edge therapies to pancreatic cancer patients.

Project Overview

Immunotherapy is not yet effective in pancreatic cancer because this type of tumor expresses high level of transforming growth factor beta (TGF-beta). The TGF-beta serves to both block immune cells at the site of the tumor as well as recruit other suppressive cells, promoting both tumor growth and evasion. This project will isolate tumor-infiltrating lymphocytes (TILs) which are specific killers of the tumor and expand them in the laboratory. After an evaluation of this approach, the research team will assess the efficacy of these altered TILs in preclinical models of pancreatic cancer. This new approach will hopefully be implemented in a clinical trial in the second phase.

Team Leaders

Patrick Hwu, M.D.
University of Texas/MD Anderson Cancer Center

Dr. Patrick Hwu is a tumor immunologist focused on vaccines, adoptive T-cell therapies, and immune resistance. His research and clinical efforts have led to insights and advances in the understanding of the interactions between tumors and the immune system, and the development of cellular therapies. Several novel, ongoing clinical trials have resulted based on his group’s work, which include a trial of T-cells modified with chemokine receptor genes to enhance their migration to the tumor. Most recently, his preclinical studies have focused on combinations of immune checkpoint blockade and T-cell therapy, as well as rational combinations of targeted therapies and immunotherapies. Both of these concepts are being moved into the clinic to improve treatment outcomes for our patients. Currently, Dr. Hwu holds the Sheikh Mohammed Bin Zayed Al Nahyan Distinguished University Chair at MD Anderson Cancer Center.

For more information, please click here.

Chantale Bernatchez, Ph.D.
University of Texas/MD Anderson Cancer Center

Dr. Bernatchez’s interest is immunotherapy of cancer with a special emphasis on T-cell therapy utilizing tumor infiltrating lymphocytes. Her lab conducts translational research where human primary cells from cancer patients (tumors or immune cells) are interrogated to find markers of response to T-cell therapy or other immunotherapies. These studies will help us define which population of patient is more susceptible to respond to TIL therapy and also will provide insights on how the therapy can be improved. Dr. Bernatchez is currently developing a new method to expand the T-cells ex-vivo (experimentation or measurements done in or on tissue from an organism in an external environment with minimal alteration of natural conditions).

For more information, please click here.

Cliona Rooney, Ph.D.
Baylor College of Medicine

Dr. Rooney is an immunovirologist with an extensive background in viral and tumor immunology. For the past 20 years, she has investigated the efficacy of virus and tumor-specific T-cells for the prophylaxis and treatment of virus-associated diseases and other malignancies, including EBV-and HPV-associated malignancies, neuroblastoma and osteosarcoma. Her longstanding research interest in tumor immunology and her successful record in conducting laboratory research and translating it to the clinic makes her extremely well qualified to direct the current project.

For more information, please click here.

Project Overview

The team recently showed that pancreatic cancer cell survival relies upon both the RAS pathway and autophagy (a process that deals with degradation of cells in the body). They will determine the mechanism by which the RAS pathway regulates autophagic processes in order to identify potential biomarkers for disease prediction as well as new autophagy inhibitors for therapeutic testing. In this regard, trametinib, a chemotherapy that slows the growth of cancer cells, along with hydroxycholoquine, an inhibitor of autophagy (T/HCQ) will be tested in a clinical trial of pancreatic cancer patients. Encouraging results from this trial will propel them towards Round 2 of this grant, where they would set up a multi-institution Phase III trial for the T/HCQ combination therapy.

Team Leaders

Martin McMahon, Ph.D.
University of Utah/Huntsman Cancer Institute

Dr. McMahon joined the faculty of the Department of Dermatology and the Huntsman Cancer Institute of the University of Utah as the Cumming-Presidential Professor of Cancer Biology and the Senior Director for Preclinical Translation. Research in the McMahon Lab focuses on the importance of RAS effectors, such as the RAF family of protein kinases and phosphoinositide 3’ (PI3’)-kinases in the aberrant physiology of cancer cells. To do so, the lab employs genetically engineered mouse models of human cancer, patient-derived xenografts (PDXs) and cultures of cancer cells in combination with various genetic or pharmacological to explore how signaling pathways contribute to cancer cell initiation, progression, and response to therapy.

For more information, please click here.

Eric Collisson, M.D.
University of California San Francisco

Dr. Collisson is a medical oncologist with a specific interest in the genomics of cancer. His laboratory uses a variety of techniques to interrogate three basic themes in the biology and clinical behavior of these deadly cancers: (1) intra-patient tumor heterogeneity at the temporal and anatomic levels, (2) inter-patient heterogeneity between different patients, and (3) tumor-microenvironmental interactions. Dr. Collisson uses a combination of genetically engineered mouse models, cell lines, and clinically derived samples to interrogate multiple genomic outputs with a focus on genomic DNA and mRNA.

For more information, please click here.

Project Overview

Pancreatic cancer is known to exhibit deficiencies in DNA repair, therefore therapies targeting this vulnerability show promise. This team proposes to develop DNA repair targeted therapies for use as single and combination agents. The team will test the therapies in both preclinical models of patient derived xenograft (PDX) mouse models and patient-derived pancreatic cancer tumors organoid cultures. These pre-clinical models will allow the team to establish both the feasibility of clinical trials for targeted DNA repair therapies and develop biomarkers intended to aid in the identification of pancreatic cancer patient sub-populations that would be the most likely to benefit from these therapies.

Team Leaders

Alan D. D’Andrea, M.D.
Dana-Farber Cancer Institute

The D’Andrea laboratory at the Dana-Farber Cancer Institute is interested in the molecular events involved in normal blood cell formation and in the molecular cause of leukemia and other cancers. His laboratory examines molecular signaling pathways and the resulting DNA damage response in mammalian cells. These pathways are often disrupted in cancer cells, accounting for chromosome instability and increased gene mutation frequency in human tumors. The practical application of D’Andrea’s research includes genetic diseases in humans. His primary focus is the molecular pathogenesis of human chromosome instability syndromes: Fanconi anemia (FA), ataxia-telangiectasia (AT), and Bloom syndrome (BS).

For more information, please click here.

James M. Cleary, M.D., Ph.D.
Dana-Farber Cancer Institute

Dr. Cleary’s career is focused on phase 1 and proof-of-mechanism clinical trials that are testing new targeted therapies and novel therapeutic strategies. He is particularly interested in new drug development for gastrointestinal malignancies. Currently, Dr. Cleary is developing several protocols appropriate for specific molecularly defined patient cohorts, including those whose tumors are dependent on EGFR, mutant K-Ras and mutant B-Raf, respectively. He also interacts with Dana-Farber translational researchers to understand and develop predictors of sensitivity and resistance to targeted agents that can be incorporated into patient selection for trials.

For more information, please click here.

Project Overview

The team proposes to utilize the immune system in order to target cells with a mutant KRAS gene, which causes the majority of pancreatic cancer. They have developed a system to isolate T immune cells from patients with receptors that recognize the mutant KRAS protein. They will validate the T-cells from these patients to ensure they only function against the mutated form of KRAS and not the normal KRAS. The final goal of the project is to test these T-cells in the clinic on pancreatic cancer patients which would be the second phase of this research.

Team Leaders

Robert Vonderheide, M.D., Ph.D.
University of Pennsylvania

Dr. Vonderheide is the co-leader of the Immunobiology Program, the Vice Chief for Research, the Hanna Wise Professor in Cancer Research, and the Director of the Abramson Cancer Center at the University of Pennsylvania. He is an expert in immunobiology, and his work explores how CD40, GM-CSF, PD-1, CTLA-4, and CD25 regulate the tumor environment and immune activity. He has also helped translate his work into novel immunotherapies including vaccines, antibodies, and adoptive T-cells which have been used to treat patients with melanoma, pancreatic cancer and other cancers. In addition to serving as a member of the Cancer Research Institute’s Scientific Advisory Council, Dr. Vonderheide serves on the CLIP Grant Review Committee and is a member of the Cancer Research Institute’s Clinical Leadership Committee. Publications include those in high-impact journals such as Nature, Science, Cell, and the New England Journal of Medicine.

For more information, please click here.

Elizabeth Jaffe, M.D.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Dr. Jaffee is an international leader in the development of immune based therapies for pancreatic and breast cancers. She is deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; associate director of the Bloomberg Kimmel Institute for Cancer Immunotherapy at Johns Hopkins; the Dana and Albert “Cubby” Broccoli professor of oncology; professor of pathology at the Johns Hopkins University School of Medicine; active staff in oncology at the Johns Hopkins Hospital; associate director for translational research, co-director of gastrointestinal cancer and diseases program, co-director of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care; and member of the faculty, Graduate Programs in Immunology, Cellular and Molecular Medicine, and Pharmacology, at the Johns Hopkins University School of Medicine. Additionally, she is the current president of the American Association for Cancer Research (AACR) and serves on numerous other boards and committees. She is also co-chair of Cancer Moonshot, an initiative of the National Cancer Institute focused on making more therapies available to more patients and improving our ability to prevent cancer and detect it at an early stage. Dr. Jaffee’s research is focused on the development of novel vaccine approaches that overcome immune tolerances to cancers, and she currently holds six vaccine patents.

For more information, please click here.

Project Overview

Radiotherapy is a cancer treatment mediated through the use of radiation to kill cancer cells. This can be done externally, using machines, or internally, through the introduction of radioactive materials into the patient. The radiation damages cancer cells, which are unable to repair themselves and die. This team proposes to use the integrin aVb6, which is significantly expressed in pancreatic cancer as a target for peptide radionuclide therapy. They have already shown the ability to use this integrin target in order to image metastatic pancreatic cancer lesions in the liver and lung. This team proposes to use the already developed imaging construct and combine it with Lutetium-177, which emits radiation in order to kill the cancer cells. For the initial phase of this grant, they plan to develop this compound and perform all the preclinical testing needed to determine therapeutic efficacy, as well as the writing and submission of IND documents for the first-in-human therapy trial. In the second phase, they want to move into a multisite therapeutic clinical trial for patients with advanced pancreatic cancer.

Team Leader

Julie Sutcliffe, Ph.D.
University of California Davis

Dr. Sutcliffe’s research involves the design, synthesis and in vivo (inside a living organism) evaluation of targeted molecular imaging agents with a focus on PET. Her group has developed rapid radiolabeling technologies using both solid-phase and solution-phase chemistries to incorporate the short half-life PET radionuclide 18F into peptides. Her group applies radiolabeled peptides to target cell surface receptors in vivo using small animal imaging. Major cell surface receptors of interest include the integrin receptors alpha(v)beta(3) and alpha(v)beta(6). Integrins are cell surface glycoproteins involved in cell-cell and cell-extracellular matrix interactions. Their over expression has been associated with many diseases including cancer. In particular, alpha(v)beta(6) is expressed at low or undetectable levels on normal tissue and is upregulated on many cancers including oral squamous cell carcinoma, breast cancer, pancreatic cancer and has recently been identified as a marker of prognosis in colon and lung cancer. In vivo imaging of this receptor could therefore have a significant impact on patient diagnosis, care and management. Peptides are synthesized using standard Fmoc chemistries, screened in vitro for affinity and selectivity and subsequently radiolabeled and screened in vivo using small animal imaging.

For more information please click here

Richard Bold, M.D.
University of California Davis

A researcher as well as a surgical oncologist, Dr. Bold is an expert in pancreatic and hepatobiliary cancers, breast cancer and the application of minimally invasive surgical techniques for patients with cancer. He has implemented a variety of minimally invasive surgical techniques to treat patients with benign or malignant tumors. Dr. Bold is a key member of a multidisciplinary breast cancer research team involving experts from radiology, nuclear medicine, and biomedical engineering working to improve breast cancer detection and better guide surgical intervention. He also oversees an active basic-science laboratory investigating mechanisms of resistance to traditional chemotherapy as well as testing new treatments for detecting and treating cancer. Dr. Bold is an integral member of the Clinical Trials Group at the UC Davis Comprehensive Cancer Center.

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Project Overview

This team has discovered that tumors containing the KRAS oncogene are sensitive to inhibition of SHP2, a protein that mediates the KRAS growth-promoting signal responsible for cancer cell growth. The team has also shown that inhibition of MEK, a different RAS target, can achieve an even better control of tumor growth. Based on these results, this team proposes to test a combination therapy consisting of SHP2 and MEK inhibitors in a variety of pre-clinical mouse models. The results of these preclinical studies will be key in designing successful Phase 1 clinical trial of the promising combination therapy of SHP2 and MEK inhibitors in pancreatic cancer.

Team Leaders

Rene Bernards, Ph.D.
Netherlands Cancer Institute

Combination therapies can help fight therapy resistance, but with an arsenal of over 1000 cancer drugs in clinical development, the number of possible combinations seems nearly endless. Dr. Bernard employs functional genetic screens to find powerful combinations of cancer drugs by exploiting the concept of “synthetic lethality.” Using RNA interference-based genetic screens with collections of shRNAs that target drugable gene families, he searched for genes whose inactivation is particularly synergistic with clinically-relevant cancer drugs. Such screens can identify drug combinations that are far more powerful than the sum of the two single agents. Dr. Bernard aims to bring such rationally-designed combinations to the cancer clinic.

For more information, please click here.

Hana Alguel, M.D., Ph.D.
Klinikum rechts der Isar, University Hospital, Munich

Dr. Alguel’s area of research is aimed at analyzing molecular mechanisms underlying spontaneous and inflammation-associated pancreatic carcinogenesis. Findings relating to gene mutations and signal transduction pathways are of great importance in developing new and innovative therapies for human patients with these conditions. Dr. Alguel’s team is also studying changes in metabolism, such as obesity or diabetes mellitus, which are important risk factors in the development of pancreatic cancer. Additionally, they are exploring cachexia which is strongly associated with pancreatic cancer and provides additional support for the relationship between metabolism and pancreatic cancer. Autophagy and macropinocytosis have emerged as intracellular regulators of metabolism and are their influence on cachexia is being thoroughly evaluated through in vivo mouse models of PDAC. Insight gained from these experiments may help to identify new therapeutic targets.

For more information, please click here.

Jan Schellens, M.D., Ph.D.
Netherlands Cancer Institute

Dr. Schellens, studied chemistry and medicine. He is board certified Medical Oncologist and Clinical Pharmacologist. He is head of the Department of Clinical Pharmacology of the Division of Medical Oncology of the Netherlands Cancer Institute and professor of Clinical Pharmacology at Utrecht University. His main research interests include early clinical trials and translational research

focused on targeted therapy and immunotherapy development and validation of biomarkers for clinical research; personalized therapy, focused on pharmacogenotyping; novel drug development focus on oral development of taxanes; and drug repurposing. Dr. Schellerns is currently the principal investigator of 63 early clinical and pharmacological trials.

For more information, please click here.

Project Overview

Pancreatic cancer stem cells may drive tumor growth and progression via retinoic acid receptor-related orphan receptor gamma (“ROR gamma”), a nuclear hormone receptor shown to be enriched in pancreatic cancer stem cells. These receptors have played a critical role in tumor growth and progression. This research team proposes to carry out preclinical studies in genetically engineered and xenograft mouse models to discover whether ROR gamma inhibitors can block the growth and progression of pancreatic cancer. As ROR gamma inhibitors are already in clinical trials for autoimmune diseases, there is potential for quick translation to the clinic, making this research area very promising for pancreatic cancer treatment.

Team Leaders

Tannishtha Reya, Ph.D.
University of California San Diego

Dr. Reya is a Professor in the Department of Pharmacology, a member of the Sanford Consortium for Regenerative Medicine and co-director of the Stem Cell Program at the Moores Comprehensive Cancer Center. Dr. Reya has made key contributions to the field of cancer biology by defining the signals that control stem cell growth, and how these signals are subverted to drive cancer progression and therapy resistance. This includes demonstration that Wnt and Hedgehog signaling are key players in promoting resistance and residual disease in myeloid leukemia. She contributed to the discovery that regulators of asymmetric division such as the stem cell determinant Musashi, are key drivers of aggressive cancers, and important targets for diagnostics and therapy. Dr. Reya has received several awards, including the Leukemia and Lymphoma Society Scholar award, the Presidential Early Career Award for Scientists and Engineers and the Pioneer Award from the National Institutes of Health.

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Andrew Lowy, M.D.
University of California San Diego

Dr. Lowy is a professor in the Department of Surgery and chief of the Division of Surgical Oncology at UC San Diego School of Medicine. Dr. Lowy is recognized worldwide for his expertise in pancreatic cancer surgery and in the management of complex gastrointestinal cancers. He is also known for investigating novel cancer treatments, including heated intraperitoneal chemotherapy (HIPEC), to treat advanced abdominal cancers. He currently serves as the surgical principal investigator for the largest pancreatic cancer clinical trial ever conducted in the United States.

For more information please click here .

Margaret Tempero, M.D.
University of California San Francisco

Dr. Tempero works at the UCSF Pancreas Center and she is leader of the UCSF Pancreas Cancer Program where she investigates the area of investigational therapeutics for pancreatic cancer.

She was a pioneer in the use of antibody-based therapies and helped develop the fixed dose rate concept for gemcitabine. Dr. Tempero has served as the Chair of the NCCN Guidelines Panel on Pancreatic Cancer since 2000 and has also served as co-chair on the Pancreas Task Force Tissue Acquisition Working Group for the NCI intergroup.

For more information please click here.

SU2C-Lustgarten Foundation-SITC Pancreatic Cancer Convergence Research Team

Computational Deconstruction of Neoantigen-TCR Degeneracy for Cancer Immunotherapy

Project Overview

The goal of this project is to understand how a patient’s immune system can lead to long-term survival. Using DNA sequencing, computer science and immunological techniques, researchers are working to understand why immune cells from long-term survivors recognize specific and unique mutations. They will then use this information to develop a method for creating vaccines to treat pancreatic cancer.

Team Leaders

Vinod Balachandran, M.D.
Memorial Sloan Kettering Cancer Center

Dr. Balachandran is a member of the David M. Rubenstein Center for Pancreatic Cancer Research. He is a surgical oncologist who specializes in treating people with both benign and cancerous diseases of the pancreas, bile duct, gallbladder, and liver. In addition to performing surgeries and caring for patients, Dr. Balachandran conducts research to identify new ways to use the immune system to fight pancreatic cancer and has received numerous awards for his work. He is the principal investigator on several projects.

For more information, please click here.

Benjamin Greenbaum, Ph.D.
Icahn School of Medicine at Mount Sinai Hospital

Dr. Greenbaum is Assistant Professor of Medicine, Hematology, Medical Oncology, Pathology and Oncological Sciences at Mount Sinai. He is a theoretical physicist working in quantitative biology at the intersection of cancer research, immunology, evolutionary theory, and virology. His lab uses tools from physics, mathematics and computer science to study the role of the immune system in several cancers. The areas they study include the interaction of host tumoral RNA with the innate immune system, the role of neoantigens in the evolution of tumors both generally and in response to therapy, and the role of endogenous and exogenous viruses in cancer. In addition to shedding light on these scientific issues, they are working to translate their work into clinically impactful results in cancer immunotherapy.

For more information, please click here.

SU2C-Lustgarten Foundation Pancreatic Cancer Interception Research Team

Developing Novel Approaches to Detect and Treat Early Pancreatic Cancer

Project Overview

This research is using a comprehensive approach for patients with borderline resectable (operable) and locally advanced pancreatic cancer. The objective is to demonstrate that a new treatment combination — the addition of losartan, a medication used for high blood pressure, combined with FOLFIRINOX, a current standard of care therapy, will shrink a patient’s tumors enough that he/she will then become eligible for surgery to remove the tumor. They test another treatment combination which consists of chemotherapy, losartan and an immunotherapy treatment called nivolumab before surgery.

Team Leaders

Alec C. Kimmelman, M.D., Ph.D.
New York University Langone Medical Center

Dr. Kimmelman is the chair of the Department of Radiation Oncology at NYU Langone, where he specializes in gastrointestinal cancers, including pancreatic, esophageal, stomach, rectal and anal cancer. His department uses the latest and most advanced technologies to treat people who have these types of cancer.
His lab work focuses on understanding the biology of pancreatic cancer. In particular, his team focuses on the unique metabolism of pancreatic cancer to understand how it uses various fuel sources to power its growth. By targeting the way pancreatic cancer uses fuel and creates building blocks for growth, Dr. Kimmelman and his team hope to develop novel therapeutic approaches. His research is paving the way for multiple clinical trials that will involve the testing of these new therapies.
He serves on the editorial boards of several leading scientific journals and has published more than 50 articles.

For more information, please click here.

David P. Ryan, M.D.
Massachusetts General Hospital

Dr. Ryan is Chief, Hematology-Oncology, and Clinical Director, MGH Cancer Center.
He has been named to America’s Top Doctors eight times. He is an authority on the treatment of gastrointestinal cancers and designs and conducts clinical trials for patients with gastrointestinal cancers. His expertise has been recognized by membership in leading national committees, including clinical task forces for the National Cancer Institute and the National Comprehensive Cancer Network.

For more information, please click here.

SU2C-Lustgarten Foundation Pancreatic Cancer Interception Dream Team

Intercepting Pancreatic Cancer in High-Risk Cohorts

Project Overview

This team is developing a screening test using machine learning techniques to identify and diagnose pancreatic lesions currently not detectable with existing technology. They are seeking to develop a first-in-human vaccine to prevent or stop the development of pancreatic cancer in individuals with an inherited predisposition.

Team Leaders

Michael G. Goggins, M.B.B. Ch., M.D.
Johns Hopkins University

Dr. Goggins is a professor of pathology, medicine and oncology at the Johns Hopkins University School of Medicine. He serves as director of the Pancreatic Cancer Early Detection Laboratory and is an attending physician in medicine in the Division of Gastroenterology and Hepatology at The Johns Hopkins Hospital, as well as a molecular biologist.
Dr. Goggins oversees research that focuses on gene expression patterns of pancreatic cancers using microarray technology. His lab is also studying DNA methylation patterns looking for genes that are methylated in pancreatic cancer, but not in normal cells. DNA methylation is an epigenetic mechanism used by cells to control gene expression.
Dr. Goggins is a member of the Royal College of Physicians and the European Board of Gastroenterology. He sits on the editorial boards of Gut, Clinical Gastroenterology and Hepatology, and Cancer Biology and Therapy.

For more information, please click here.

Scott M. Lippman, M.D.
University of California, San Diego

Dr. Lippman is the director of the Moores Cancer Center at the University of California, San Diego and Professor of Medicine at UC San Diego School of Medicine. He has more than 25 years of experience as a principal investigator of translational research involving investigator-initiated clinical trials and maintains an active clinical practice. As a clinician, he is well-respected by his peers, with recognition in every major “Top Doctor” listing including U.S. News & World Report. His research interests include clinical trials using molecular targets and markers for cancer prevention and therapy. He has authored more than 350 publications in high-impact journals and has received many awards.

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Anirban Maitra, M.B.B.S.
University of Texas MD Anderson Cancer Center

Dr. Maitra is Professor of Pathology and Translational Molecular Pathology at UT MD Anderson Cancer Center, and Scientific Director of the Sheikh Ahmed Bin Zayed Center for Pancreatic Cancer Research. Over the past decade, his group has made several seminal observations in the biology and genetics of pancreatic cancer. His laboratory has access to large numbers of well annotated samples of pancreatic adenocarcinomas and precursor lesions, as well as human patient derived xenograft models. He also has extensive expertise with genetically engineered mouse models of pancreatic cancer and with experimental therapeutics and drug development for this disease.

For more information, please click here.

SU2C Catalyst® Research Grant–Merck Supported Project Targeting VDR to Make Pancreatic Cancer Competent for Immunotherapy

Project Overview

Previous research from this team suggests that therapies targeting the vitamin D receptor will perhaps “unmask” the pancreatic tumors and allow the immune cells to reach them, creating the possibility that immunotherapies will be effective. The goal of this research is
to test if targeting the vitamin D receptor will unlock the potential of immunotherapies to kill pancreatic cancer tumor cells and potentially establish a therapeutic combination for controlling advanced pancreatic cancer, extending patient survival, and reducing patient side effects.

Team Leader

Daniel D. Von Hoff, M.D., F.A.C.P.
Translational Genomics Research Institute (TGen)
HonorHealth

Dr. Von Hoff is Physician-in-Chief and Distinguished Professor at the Translational Genomics Research Institute (TGen) in Phoenix. He also holds the Virginia G. Piper Distinguished Chair for Innovative Cancer Research at HonorHealth Clinical Research Institute and Medical Director of Research at McKesson Specialty Health and the Chief Scientific Officer for US Oncology Research specializing in Phase I clinical trials. He is a Professor of Medicine, Mayo Clinic Scottsdale, AZ as well.
Dr. Von Hoff’s major interest is in the development of new anti-cancer agents, both in the clinic and in the laboratory. His clinical trial work has led to the approval of three of the four FDA-approved drugs to treat pancreatic cancer. Dr. Von Hoff has published more than 675 papers, 140 book chapters and over 1,170 abstracts. Dr. Von Hoff received the 2010 David A. Karnofsky Memorial Award from the American Society of Clinical Oncology for his outstanding contributions to cancer research leading to significant improvement in patient care.

For more information, please click here.

SU2C-Lustgarten Foundation Translational Research Team

Chimeric Antigen Receptor T-Cell (CAR T) Therapy for Pancreatic Cancer

Project Overview

This research team is studying CAR T-cell immunotherapy in metastatic pancreatic cancer patients, looking for changes in DNA “on and off switches” (epigenetic changes) following treatment with CAR T. The team ultimately seeks to identify epigenetic changes for better understanding of why certain patients respond to treatment compared to non-responders.

Team Leaders

Shelley L. Berger, Ph.D.
University of Pennsylvania

Dr. Berger is the Daniel S. Och University Professor at University of Pennsylvania and is a faculty member in the Cell & Developmental Biology Department and the Genetics Department in the Perelman School of Medicine, as well as the Biology Department in the School of Arts and Sciences. Dr. Berger also serves as Director of the Epigenetics Program at the Perelman School of Medicine. Over its history, research in Dr. Berger’s lab has uncovered numerous chromatin enzymes and has addressed fundamental questions on their mechanisms in modifying both histones and DNA binding activators (i.e. the tumor suppressor, p53) in transcription. These findings have contributed significantly to the broad interest and focus on epigenetics in biomedical research. The lab has published more than 170 papers and reviews, including many in high-impact journals such as Nature, Science, Cell, and Genes & Development.

For more information, please click here.

Carl H. June, M.D.
University of Pennsylvania

Dr. June is the Richard W. Vague Professor in Immunotherapy, the Director of the Center for Cellular Immunotherapies and Parker Institute for Cancer Immunotherapy at the University of Pennsylvania Perelman School of Medicine. The June Laboratory provides researchers with the tools they need to translate laboratory insights into safe and effective cancer therapies.
Dr. June has been a pioneer in the field of immunotherapy, most widely known for the development of T-cell therapy for cancer. In the 1980s, his lab discovered the CD28 molecule as the major control switch for T-cells. A few years later, he tested the ability to culture genetically modified CAR-Ts in humans, discovering the cells could engraft and persist in patients with HIV/AIDS for years. His work led to the development and commercialization of tisagenlecleucel, the first FDA-approved gene therapy.

For more information, please click here.

E. John Wherry, Ph.D.
University of Pennsylvania

Dr. Wherry is the Director of the Institute for Immunology and a Professor of Microbiology at the Perelman School of Medicine at the University of Pennsylvania. Dr. Wherry’s discoveries include insights into how changes in gene expression affect T-cell exhaustion, which is a loss of immune function that occurs as a result of chronic viral infection and cancer. Normally, during a short-term infection, such as the flu, immune cells handily eliminate the offending pathogen. However, in long-term, chronic infections such as cancer, T-cells and the opposing pathogen or malignancy engage in a continuous struggle, and over time the T-cells become “exhausted,” giving cancer or the pathogen the edge.

Dr. Wherry is one of the most frequently cited researchers in his field by and was named one of America’s Young Innovators by Smithsonian magazine (2007). He serves on many scientific advisory panels and editorial boards.

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SU2C-Cancer Research UK-Lustgarten Foundation Pancreatic Cancer Dream Team

Reprogramming of Transcriptional Circuitry to Control Pancreatic Cancer

Project Overview

This team is building on previous research which found that vitamin D receptors play an important role in the effectiveness of chemotherapy. They are studying vitamin D receptors to determine if they are effective “super-enhancers” which improve patient response to chemotherapy.

Team Leaders

Gerard I. Evan, Ph.D., F.R.S.
University of Cambridge

Dr. Evan serves as Head of the Department of Biochemistry at the University of Cambridge. Dr. Evan is a Gerson and Barbara Bass Baker Distinguished Professor of Cancer Biology at the University of California, San Francisco. He is also co-leader of the Cell Cycling and Signaling Program at the UCSF Comprehensive Cancer Center, which he helped create in 1999. His research focuses on the molecular basis of cancer. To address this problem, he has developed a novel class of genetically engineered mice in which individual oncogenes and/or tumor suppressor genes may be systemically toggled off and on, reversibly and at will, in vivo.

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Ronald M. Evans, Ph.D.
Salk Research Institute for Biological Studies

Dr. Evans is a professor and biologist at the Salk Institute for Biological Studies in La Jolla, California and a Howard Hughes Medical Institute Investigator. Dr. Evans is an authority on hormones, both their normal activities and their roles in disease. His research focuses on the function of nuclear hormone signaling and metabolism. His lab has discovered that a chemically modified form of vitamin D might offer a new approach to treating pancreatic cancer. The vitamin D derivative makes tumor cells vulnerable to chemotherapy and more sensitive to the body’s immune system. With clinicians at the University of Pennsylvania, Dr. Evans’ team launched a clinical trial to test this drug in pancreatic cancer patients, and this trial is ongoing.

For more information about the clinical trial, please click here.

In 2003, he was awarded the March of Dimes Prize in Developmental Biology and in 2004 he received the Albert Lasker Award for Basic Medical Research. He is also a recipient of the Harvey Prize (2006), the Gairdner Foundation International Award (2006), the Albany Medical Center Prize (2007) and the Wolf Prize in Medicine (2012).

He is one of the most cited living biologists and has been a member of the National Academy of Sciences since1989. Dr. Evans serves as a Lustgarten Foundation Distinguished Scholar as well.

For more information, please click here.

Daniel D. Von Hoff, M.D., F.A.C.P.
Translational Genomics Research Institute (TGen)
HonorHealth

Dr. Von Hoff is Physician-in-Chief and Distinguished Professor at the Translational Genomics Research Institute (TGen) in Phoenix. He also holds the Virginia G. Piper Distinguished Chair for Innovative Cancer Research at HonorHealth Clinical Research Institute and Medical Director of Research at McKesson Specialty Health and the Chief Scientific Officer for US Oncology Research specializing in Phase I clinical trials. He is a Professor of Medicine, Mayo Clinic Scottsdale, AZ as well.
Dr. Von Hoff’s major interest is in the development of new anti-cancer agents, both in the clinic and in the laboratory. His clinical trial work has led to the approval of three of the four FDA-approved drugs to treat pancreatic cancer. Dr. Von Hoff has published more than 675 papers, 140 book chapters and over 1,170 abstracts. Dr. Von Hoff received the 2010 David A. Karnofsky Memorial Award from the American Society of Clinical Oncology for his outstanding contributions to cancer research leading to significant improvement in patient care.

For more information, please click here.

SU2C-National Science Foundation-Lustgarten Foundation Convergence Research Team

Liberating T-Cell Mediated Immunity to Pancreatic Cancer

Project Overview

This team’s long-term goal is to understand the factors that lead to resistance or response in patients treated with various forms of cancer immunotherapy. In particular, the goals are to investigate patient epigenetic variation that influences the response to immunotherapy and to use epigenetic therapeutics alone or in combination with immunotherapy to inhibit tumor progression as well as to overcome resistance to immunotherapy.

Team Leader

Peter J. O’Dwyer, M.D.
University of Pennsylvania

Dr. O’Dwyer is an oncologist in Philadelphia and is affiliated with multiple hospitals in the area, including the Hospital of the University of Pennsylvania and the Presbyterian Medical Center of Pennsylvania.. Dr. O’Dwyer is a Fellow in the American College of Physicians, and a member of the American Boards of Pediatrics, American Boards of Internal Medicine, and Subspecialty Boards in Medical Oncology.

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SU2C-Lustgarten Foundation Pancreatic Cancer Dream Team

Transforming Pancreatic Cancer to a Treatable Disease

Project Overview

This Dream Team is investigating combinations of treatments, focused on different and unique pathways involved in the immune response to treatment found in the tumor and the stroma, which is the supportive tissue surrounding the tumor.

Team Leaders

Elizabeth M. Jaffee, M.D.
Johns Hopkins University

Dr. Jaffee is an international leader in the development of immune based therapies for pancreatic and breast cancers. She is deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; associate director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins; the Dana and Albert “Cubby” Broccoli professor of oncology; professor of pathology at the Johns Hopkins University School of Medicine; active staff in oncology at the Johns Hopkins Hospital; associate director for translational research, co-director of gastrointestinal cancer and diseases program, co-director of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care; and member of the faculty, Graduate Programs in Immunology, Cellular and Molecular Medicine, and Pharmacology, at the Johns Hopkins University School of Medicine. Additionally, she is the current president of the American Association for Cancer Research (AACR) and serves on numerous other boards and committees. She is also co-chair of Cancer Moonshot, an initiative of the National Cancer Institute focused on making more therapies available to more patients and improving our ability to prevent cancer and detect it at an early stage.
Dr. Jaffee’s research is focused on the development of novel vaccine approaches that overcome immune tolerances to cancers, and she currently holds six vaccine patents.

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Robert H. Vonderheide, M.D., D. Phil.
Abramson Cancer Center, University of Pennsylvania

Dr. Vonderheide is the co-leader of the Immunobiology Program, the vice chief for Research, the Hanna Wise Professor in Cancer Research, and the director of the Abramson Cancer Center at the University of Pennsylvania. He is an expert in immunobiology, and his work explores how CD40, GM-CSF, PD-1, CTLA-4, and CD25 regulate the tumor environment and immune activity. He has also helped translate his work into novel immunotherapies including vaccines, antibodies, and adoptive T-cells which have been used to treat patients with melanoma, pancreatic cancer and other cancers. In addition to serving as a member of the Cancer Research Institute’s Scientific Advisory Council, Dr. Vonderheide serves on the CLIP Grant Review Committee and is a member of the Cancer Research Institute’s Clinical Leadership Committee. Publications include those in high-impact journals such as Nature, Science, Cell, and the New England Journal of Medicine.

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