Immunotherapy for Pancreatic Cancer

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  • Pancreatic Cancer
  • Treatment Options
  • CRI's Impact
  • Clinical Trials

How is Immunotherapy Changing the Outlook for Patients with Pancreatic Cancer?

Reviewed By: Elizabeth Jaffee, M.D.
Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD

Pancreatic cancer is the most lethal cancer, and new therapies are urgently needed to impact pancreatic cancer treatment and to extend and save pancreatic cancer patients’ lives. Immune-based strategies to treat pancreatic cancer during the early stages of development, as well as new immunological approaches to treat advanced disease, are showing significant promise where other approaches have failed. This page features information on pancreatic cancer and immunotherapy clinical trials for pancreatic cancer patients, and highlights the Cancer Research Institute’s role in working to bring effective immune-based cancer treatments to pancreatic cancer patients.

Pancreatic cancer is the fourth-leading cause of cancer-related death in the United States, with a 5-year survival rate of less than 7%. Compared to other cancers, it shows marked resistance to conventional forms of chemotherapy, and there are limited capabilities to diagnose and treat the disease in its earliest stages. No current treatment option has demonstrated long-term benefit in patients with advanced disease who are not eligible for surgery—which represents the majority (80%) of pancreatic cancer cases.

Urgent Need

Urgent Need: Pancreatic ductal adenocarcinoma (PDA), which accounts for more than 90% of pancreatic cancer cases, is highly lethal; for all stages combined, the 1- and 5-year relative survival rates are 27% and 7%, respectively, making it the only cancer with an overall 5-year survival rate in the single digits. Even for those people diagnosed with local disease, 5-year survival is only 27%. More than half of patients are diagnosed at a distant stage, for which 5-year survival is 2%.

Incidence and Mortality: Each year more than 53,070 people in the United States will be diagnosed with pancreatic cancer, and more than 41,780 will die. Worldwide, more than 337,000 people will be diagnosed, and more than 330,000 will die of the disease. The incidence of pancreatic cancer is rising, and some reports project that the number of new pancreatic cancer cases and pancreatic cancer deaths will more than double by 2030.

Detection/Diagnosis: Pancreatic cancer is very difficult to detect or to diagnose at early stages of disease. It often develops without early symptoms, there is no widely used method for early detection, and, although some risk factors have been identified (such as tobacco use, family history of pancreatic cancer, and a personal history of pancreatitis, diabetes, or obesity), few patients diagnosed with pancreatic cancer have identifiable risk factors.


The only curative treatment for pancreatic cancer is complete surgical resection. Unfortunately, fewer than 20% of patients are candidates for surgery, because pancreatic cancer is usually detected after it has spread. Cancers that cannot be treated with surgery are called “unresectable.” For those patients with localized disease and small cancers with no lymph node metastases and no extension beyond the capsule of the pancreas, complete surgical resection can yield 5-year survival rates of 18% to 24%. Approximately 80% of patients who undergo surgery eventually relapse and die from the disease, suggesting a need for effective strategies to eradicate minimal residual disease following surgery to prevent relapse.

For patients who undergo surgery, adjuvant treatment with the chemotherapy drug gemcitabine lengthens survival. The targeted anti-cancer drug erlotinib (Tarceva®) has also demonstrated a small improvement in advanced pancreatic cancer survival when used in combination with gemcitabine. More recently, combination chemotherapy with FOLFIRINOX has shown an overall survival (OS) benefit of approximately 11 months versus about 6.5 months for gemcitabine alone, and gemcitabine plus abraxane has shown an OS of 8.5 versus 6.5 for gemcitabine. Thus, for cancers that are unresectable, treatments including chemotherapy and targeted therapy may be able to control the disease and help patients live longer and feel better. Unfortunately, these treatments have not been shown to achieve longer term survival.

When Are Clinical Trials Recommended?

Because of the poor prognosis and lack of effective treatment options, for pancreatic cancer a clinical trial is nearly always preferred over existing treatment options for everything except localized tumors that can be removed surgically. Specifically, pancreatic cancer patients are encouraged to participate in clinical trials:

  • As adjuvant treatment after surgery for local disease
  • When pancreatic cancer returns after surgery
  • For unresectable disease (locally advanced cancer that cannot be treated by surgery), when the patient is in good condition (has a good performance status)
  • After first-line treatment for locally advanced cancer or metastatic, if the patient has good performance status
  • As neo-adjuvant therapy to evaluate direct treatment effects on the tumor

Go to our Clinical Trial Finder to find clinical trials of immunotherapies for pancreatic cancer that are currently enrolling patients.

CRI Contributions and Impact

CRI discoveries and ongoing work in pancreatic cancer research and treatment include:

  • A new study by former CRI predoctoral fellow Eric Lutz, Ph.D., and CRI’s Scientific Advisory Council member and clinical trial researcher Elizabeth Jaffee, M.D., found that a vaccine called GVAX could convert a “non-immunogenic” tumor into an immunogenic one in pancreatic cancer. Furthermore, they found that post-GVAX T cell infiltration resulted in up-regulation of immunosuppressive pathways, such as PD-1/PD-L1, suggesting that patients with vaccine-primed pancreatic cancer may be better candidates for immune checkpoint blockade. GVAX was first tested in 1993 by CRI Scientific Advisory Council members Drew Pardoll, M.D., Ph.D., Glenn Dranoff, M.D., Hyam Levitsky, M.D., Elizabeth Jaffee, M.D., and colleagues, who found that it could induce potent, specific, and long-lasting anti-tumor immunity in multiple cancers.
  • In 2012, Lauren Bayne, Ph.D., a former CRI predoctoral fellow at the University of Pennsylvania, and Yuliya Pylayeva-Gupta, Ph.D., a 2009-2012 CRI postdoctoral fellow at NYU Langone Medical Center, independently showed that the mutation in the KRas gene—which is mutated in nearly all pancreatic cancers—triggers expression of the immune molecule GM-CSF. They further found that tumor-derived GM-CSF recruits immature immune cells and turns them into suppressive immune cells, and that by blocking GM-CSF they could inhibit the suppressor cells and enable the immune system to fight the tumors. Because KRas mutations and tumor-promoting inflammation are associated from the earliest stages of pancreatic cancer, strategies to specifically target GM-CSF may offer the possibility of delaying or reversing inflammation-driven pancreatic cancer progression.

This hematoxylin and eosin stained slide of a surgically removed (resected) primary pancreatic tumor shows a cluster of immune cells (lymphoid aggregate) observed next to a pancreatic tumor lesion in a patient treated with a GM-CSF vaccine 2 weeks before surgical removal of the primary tumor. Immunohistochemistry of this and similar aggregates found throughout the resected tumor shows CD4+ and CD8+ T cells—aka helper T cells and killer T cells, respectively—with B cells in germinal center-like structures. (Photo courtesy of Lei Zheng and Elizabeth Jaffee, Johns Hopkins University)

  • Another approach to chimeric antigen receptor (CAR) T cell therapy involves targeting the fibroblast activation protein (FAP), which is selectively expressed by pancreatic tumor stromal cells. Scientists hypothesize that FAP+ stromal cells recruit and educate suppressive immune cells. In models, elimination of FAP+ stromal cells has been shown to enhance the efficacy of therapeutic vaccination and inhibit tumor growth. In a current study, CRI-funded graduate student Albert Lo is working to validate FAP+ stromal cells as candidate targets for pancreatic cancer immunotherapy through preclinical studies of adoptive therapy with CAR T cells modified to target FAP.
  • CRI postdoctoral fellow Ingunn M. Stromnes, Ph.D., has developed a mouse model of pancreatic ductal adenocarcinoma that is particularly good for studying this disease. Using her mouse model, Stromnes watched as pancreatic tumors developed and noticed that one type of regulatory immune cell stood out. Called granulocyte-myeloid-derived suppressor cells (Gr-MDSCs), these cells increased in number at precisely the same time that pancreatic tumors became more aggressively invasive. She discovered that the tumors were indeed attracting these Gr-MDSCs by releasing a protein called granulocyte macrophage colony-stimulating factor (GM-CSF). At the site of the tumor, the Gr-MDSCs formed a defensive barrier, preventing the immune system’s “killer” T cell from reaching the tumor. Stromnes then administered a monoclonal antibody targeted against a particular antigen found on Gr-MDSCs, selectively depleting these cells from the tumor. Once this barrier was removed, she found that the killer T cells were able to enter the tumors and launch an assault. Ultimately, the team hopes to combine their armor penetrating-approach with adoptive T cell therapy, as well as standard chemotherapy, in the hope of eradicating pancreatic cancer.
  • Studies with activating antibodies targeting the CD40 molecule have shown their ability to alter suppressive immune cells in the pancreatic cancer microenvironment, called tumor-associated macrophages (TAMs). The antibodies shift TAMs from a pro-cancer to an anti-cancer state, enabling the destruction of tumor stroma and allowing improved access by other immune cells and cytotoxic drugs. Robert Vonderheide, M.D., D.Phil., a member of CRI’s Scientific Advisory Council, showed in an early clinical trial that an antibody targeting the CD40 molecule (CP-870,893) had promise in treating patients with metastatic pancreatic cancer. Of 21 patients treated with the anti-CD40 antibody, plus the chemotherapy gemcitabine, 5 patients (24%) had a partial response and 11 patients (52%) showed stable disease, resulting in an overall clinical benefit rate of more than 75%. Treatment with the anti-CD40 antibody also demonstrated increased median progression-free survival (5.6 months v. 2.3 months with gemcitabine alone) and overall survival (7.4 months v. 5.7 months with gemcitabine alone) (NCT01456585).
  • In 2008, several CRI investigators were part of a multi-institutional preclinical study showing that treatment with the immune activating molecule interleukin 15 (IL-15), when complexed with its receptor, could trigger rapid regression of established pancreatic cancers and significantly prolong survival. They found that destruction of the cancer was mediated by killer T cells residing in the tumor rather than newly infiltrating killer T cells. This suggests that treatment with IL-15 can successfully relieve tumor-resident killer T cells from functional suppression and reactivate them to kill pancreatic cancer cells. A phase I clinical trial to test IL-15 treatment in patients with pancreatic cancer began in 2012.
  • Clinic and Laboratory Integration Program (CLIP) researcher Bruno Sainz Jr., Ph.D., is working to understand the role of the innate immune system in promoting cancer stem cells. Although the mechanisms underlying cancer development are unknown, the concept of cancer stem cells and their role in tumorigenesis has gained enormous attention over the past decade. These cancer stem cells are extremely resistant to therapy and drive tumor relapse even after aggressive chemotherapy. The laboratory has identified a protein that is highly expressed by immune cells in the stroma of pancreatic tumors, and their preliminary data strongly support a cancer stem cell-specific pro-tumorigenic role for this peptide. Their ultimate goal is to use this knowledge to develop new therapeutic strategies to eliminate cancer stem cells and thus effectively treat and cure pancreatic cancer.
Featured Patient

They get a pancreas cancer cell, kill it, hook it up to other factors, and then they inject it into you like they would any other vaccine.

Jesse C
Pancreatic Cancer  |  Diagnosed 2008
Read My Story
Featured Scientist
Bruno Sainz, Ph.D.
Universidad Autónoma de Madrid (Spain)
CLIP Investigator  |  2014
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Pancreatic Cancer Statistics

4th Leading cause of cancer-related deaths in the US
7% Overall 5-year survival rate
7 Types of immunotherapy clinical trials

Clinical Trials for Pancreatic Cancer

Several approaches to immunotherapy for pancreatic cancer have shown promise in early clinical trials. These treatments can be broken into 7 main categories: checkpoint inhibitors/immune modulators, therapeutic vaccines, adoptive cell transfer, monoclonal antibodies, oncolytic viruses, adjuvant immunotherapies, and cytokines. 

  • Checkpoint Inhibitors/Immune Modulators
  • Therapeutic Vaccines
  • Adoptive Cell Therapy
  • Monoclonal Antibodies
  • Oncolytic Virus Therapies

A promising avenue of clinical research in pancreatic cancer is the use of immune checkpoint inhibitors. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses. Several checkpoint inhibitors, targeting multiple different checkpoints, are currently in development:

Nivolumab (Opdivo®): A PD-1 Antibody +/- Ipilimumab (Yervoy®): A CTLA-4 Antibody

  • A phase I/II trial of nivolumab or nivolumab combined with ipilimumab in patients with advanced or metastatic solid tumors, including pancreatic cancer (NCT01928394).
  • A phase I/II trial of nivolumab for patients with advanced cancer, including pancreatic cancer (NCT02423954).
  • A phase I trial of nivolumab for patients with advanced cancer, including pancreatic cancer, in combination with FPA008, an antibody that inhibits colony stimulating factor-1 receptor (CSF1R), which targets immune cells (NCT02526017).
  • A phase I trial of ipilimumab (Yervoy®) and gemcitabine in treating patients with stage III-IV or recurrent pancreatic cancer that cannot be removed by surgery (NCT01473940).
  • A phase I study to test ipilimumab (Yervoy®) combined with MGA271, an antibody that targets B7-H3, in patients with refractory cancer, including pancreatic cancer (NCT02381314).

Pembrolizumab (Keytruda®, MK-3475): A PD-1 Antibody

  • A phase I/II trial for patients with advanced cancer, including pancreatic cancer, combined with PLX3397, a tyrosine kinase inhibitor of KIT, CSF1R, and FLT3 (NCT02452424).
  • A phase I/II trial for patients with resectable or borderline resectable pancreatic cancer (NCT02305186).
  • A phase I/II trial for patients with advanced cancer, including pancreatic cancer, in combination with chemotherapy (NCT02331251).
  • A phase I study for patients with refractory cancer, including pancreatic cancer, combined with MGA271, an antibody that targets B7-H3 (NCT02475213).
  • A phase I trial for patients with advanced pancreatic cancer, with Reolysin®, an oncolytic virus that is able to replicate specifically in cancer cells bearing an activated RAS pathway, and chemotherapy (NCT02620423).
  • A phase I trial for patients with advanced cancer, including pancreatic cancer, combined with defactinib, a focal adhesion kinase (FAK) inhibitor, and gemcitabine (NCT02546531).

Durvalumab (MEDI4736): A PD-L1 Antibody +/- Tremelimumab: A CTLA-4 Antibody

  • A phase I trial of durvalumab, tremelimumab, or the combination for patients with unresectable pancreatic cancer (NCT02311361).
  • A phase I study of durvalumab plus tremelimumab for patients with metastatic pancreatic cancer (NCT02639026).
  • A phase I trial of durvalumab for patients with pancreatic cancer, in combination with selumetinib, an inhibitor of MEK 1 and 2 (NCT02586987).
  • A phase I study of durvalumab plus mogamulizumab, an antibody directed against CC chemokine receptor 4 (CCR4), or tremelimumab plus mogamulizumab in patients with advanced cancer (NCT02301130).

Other Drugs

  • A phase I study to test MGD009, a B7-H3 x CD3 DART protein, in patients with unresectable or metastatic B7-H3-expressing cancer, including pancreatic cancer (NCT02628535).
  • A phase I trial of RO70097890, a CD40 antibody, for patients with newly diagnosed resectable pancreatic cancer (NCT02588443).


Cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Several trials of vaccines, given alone or with other therapies, are currently enrolling patients with pancreatic cancer:

  • A phase II trial of a vaccine that targets the NY-ESO-1 protein in patients with advanced cancer whose cancers express NY-ESO-1 (NCT01697527).
  • A phase I/II study of GVAX vaccine +/- nivolumab (Opdivo®) in patients with surgically resectable pancreatic cancer (NCT02451982).
  • A phase I trial of a dendritic cell vaccine plus standard-of-care chemotherapy for patients with resectable, borderline resectable, or locally advanced pancreatic cancer or patients with metastatic pancreatic cancer, newly diagnosed/untreated metastatic pancreatic cancer, or metastatic pancreatic cancer who have undergone prior neo-adjuvant therapy (NCT02548169).
  • A phase I study of two vaccines—one to target the TERT, which has been detected in more than 85% of all human cancers, and one to target the interleukin 12 (IL-12), which enhances immune cell activity—for patients with select tumors, including pancreatic cancer (NCT02327468).


Another major avenue of immunotherapy for pancreatic cancer is adoptive T cell transfer. In this approach, T cells are removed from a patient, genetically modified or treated with chemicals to enhance their activity, and then re-introduced into the patient with the goal of improving the immune system’s anti-cancer response. Several trials of adoptive cell transfer techniques are currently under way for patients with pancreatic cancer, including:

  • A phase II trial taking enriched tumor-infiltrating immune cells and re-infusing them in patients with metastatic digestive tract cancers, including pancreatic cancer (NCT01174121).
  • A phase II study of T cells genetically reengineered to target the NY-ESO-1 antigen in patients with NY-ESO-1-positive cancers (NCT01967823).
  • A phase I/II trial is also testing CAR T cells modified to recognize mesothelin in patients with pancreatic cancer (NCT01583686).
  • A phase I/II trial of T cells genetically reengineered to target the anti-MAGE-A3 protein in advanced cancer (NCT02111850).
  • A phase I study of T cells engineered to recognize the NY-ESO-1, MAGE-A4, PRAME, survivin, and SSX markers in patients with solid tumors, including pancreatic cancer (NCT02239861).


Monoclonal antibodies are molecules, generated in the lab, that target specific antigens on tumors. Many monoclonal antibodies are currently used in cancer treatment, and some appear to generate an immune response.

  • A phase II study of MM-141, an antibody targeting HER3 and IGF-1R, plus chemotherapy in patients with front-line metastatic pancreatic cancer (NCT02399137).
  • A phase I/II trial testing IMMU-132, an antibody-drug conjugate targeting Τrop-2, in patients with pancreatic and other cancers (NCT01631552).
  • A phase I trial of MVT-5873, an antibody against the carbohydrate antigen 19-9, in patients with pancreatic cancer (NCT02672917). CA19-9 is overexpressed on a number of different tumor cell types, and plays a key role in tumor cell survival and metastasis.


Oncolytic virus therapy uses a modified virus that can cause tumor cells to self-destruct and generate a greater immune response against the cancer.

  • A phase I/II trial of ParvOryx, an oncolytic parvovirus that infects and destroys cancer cells, in patients with metastatic, inoperable pancreatic cancer (NCT02653313).
  • A phase I trial of Reolysin®, an oncolytic virus that is able to replicate specifically in cancer cells bearing an activated RAS pathway, pembrolizumab (Keytruda®, MK-3475), a PD-1 antibody, and chemotherapy for patients with advanced pancreatic cancer (NCT02620423).

Go to our Clinical Trial Finder to find clinical trials of immunotherapies for pancreatic cancer that are currently enrolling patients.


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National Cancer Institute Physician Data Query (PDQ), American Cancer Society Facts & Figures 2016, National Comprehensive Cancer Network (NCCN) Guidelines for Patients,, CRI grantee progress reports

Updated March 2016

*Immunotherapy results may vary from patient to patient.