NFCR Translational Research: Pancreatic Cancer
Specialized Antibodies to Target Cells Around Pancreatic Cancer:
Making Immunotherapy an Effective Treatment
Daniel D. Von Hoff, M.D., FACP Translational Genomics Research Institute, Phoenix, AZ
Dr. Daniel Von Hoff, a pioneer and world-leading physician-scientist in translational medicine, has personally been involved in over 200 clinical trials. In 1985, NFCR began to fund his research that led to the first approved treatment for pancreatic cancer, the chemotherapy gemcitabine.
Currently, he is developing monoclonal antibodies to target the stellate cells surrounding pancreatic tumors. Stellate cells form fibrotic tissue and create a barrier to the attack of immunotherapy. The monoclonal antibodies bind to stellate cells and break up the fibrotic tissue to expose cancer cells to immunotherapy or other treatments.
NFCR funds are facilitating the required pre-clinical research to translate the lead antibody to clinical development stage to ultimately reach patients.
Development of Botanical Drug with Multiple Anti-Cancer Properties
Yung-Chi Cheng, Ph.D. Yale University, New Haven, CT
Dr. Yung-Chi Cheng and his team developed a four-herb formulation into YIV-906, a botanical drug with multiple anti-cancer properties that also enhance immunotherapy and chemotherapy. In previous early-stage Phase I/II clinical trials for pancreatic, colorectal, and liver cancers, YIV-906 demonstrated safety and promising efficacy with the potential to improve survival and quality of life for patients.
NFCR’s continued funding helped Dr. Cheng develop his lab’s exclusive botanical drug quality control and monitoring platform.
Since 2020, a global Phase II clinical trial is treating liver cancer patients with YIV-906 combined with a frontline drug. Since YIV-906 also protects the gastrointestinal tract from harsh side effects of many therapies, the botanical should alleviate adverse effects of the frontline drug. With success in final clinical trials, YIV-906 could become the first U.S.-approved botanical cancer drug. This would facilitate future trials of YIV-906 therapy for pancreatic cancer.
Treatment in Clinical Trials for non-Hodgkin T-cell Lymphoma Shows Promise in Pancreatic Cancer Pre-Clinical Studies
Michael B. Sporn, M.D. formerly of Geisel School of Medicine at Dartmouth, Hanover, NH
Fenretinide, a drug similar in structure to Vitamin A, may offer patients non-Hodgkin T-cell Lymphoma a life-saving treatment. Previously, former NFCR-funded scientist, Dr. Michael Sporn, researched fenretinide and proved its safety in humans for other cancers. Subsequently, the drug demonstrated safety and effectiveness in patients. non-Hodgkin T-cell Lymphoma is toxic to cancer cells by activating the cell suicide pathway (apoptosis). Scientists discovered fenretinide reactivates the immune system to complement apoptosis and it is effective in models of non-Hodgkin T-cell Lymphoma, pancreatic cancer and other cancer types. Fenretinide will soon begin Enrollment in the Phase 1 trial for non-Hodgkin T-cell Lymphoma patients. NFCR’s support for SciTech helped develop a unique delivery system for fenretinide and gain FDA approval to treat non-Hodgkin T-cell Lymphoma patients who no longer respond to their current therapy. Success in clinical trials for these patients will facilitate a future clinical trial for patients with pancreatic and other types of cancer.
Pre-clinical Development of Multi-Action Gene Therapy for Metastatic Pancreatic Cancer
Paul B. Fisher, M.Ph., Ph.D. Virginia Commonwealth University, Richmond, VA
NFCR funding since 2008 helped Dr. Paul Fisher think “outside the box” to develop IL/24 gene therapy (IL/24 is from the Interleukin gene family of immune system modulators).
He engineered IL/24 gene to cause cancer cells — at all sites in the body — to commit suicide (normal way cells die). Healthy cells are unaffected by IL/24 gene’s effects. IL/24 gene modulates the immune system to kill cancer, inhibits blood vessel formation to tumors to starve them of a vital blood supply, and sensitizes cancer to radiation, chemotherapy and immunotherapy. IL/24 gene therapy is effective in models of metastatic pancreatic cancer among other cancer types.
Dr. Fisher is bringing IL/24 gene therapy to clinical trials to benefit patients. The gene therapy is advancing through pre-clinical research first as a new treatment for fatal brain cancer, GBM (glioblastoma). This would facilitate future trials of YIV-906 for pancreatic cancer patients. IL/24 gene therapy is also effective in models of melanoma and colon, bladder, liver, and prostate cancer, among other types.
Development of New Inhibitor of Cancer Invasion into Healthy Tissue and Metastasis
Paul B. Fisher, M.Ph., Ph.D. Virginia Commonwealth University, Richmond, VA
Invasion of cancer cells into healthy tissue is a hallmark property of cancer. MDA-9/Syntenin is a pro-invasion and pro-metastatic gene discovered by Dr. Paul Fisher with NFCR funds. With leading-edge chemistry and drug design techniques, his team developed the drug, PDZ1i, to inhibit invasion and metastasis properties of MDA-9/Syntenin. PDZ1i shows profound “anti-invasive” and “anti-metastatic” activity in models of liver, pancreas, brain, lung, breast and prostate cancer and melanoma and neuroblastoma. PDZ1i works well with chemotherapy, radiation, or immunotherapy to kill cancer cells. Patients with hepatocellular cancer (HCC)—the main type of liver cancer, need effective treatments to save their lives. NFCR funds are advancing the required pre-clinical research of PDZ1i to apply for the IND (Investigational New Drug) application and gain FDA approval for a Phase 1 clinical trial for HCC patients. Success in the trial for HCC patients will facilitate future trials of PDZ1i treatment for pancreatic and other types of cancer.
BASIC RESEARCH PROJECTS
Dr. Danny Welch and his team have discovered eight metastasis suppressor genes that get turned off when cancer cells become metastatic cells. The most recent of these discoveries is the ITI5H gene that blocks metastasis of pancreatic cancer in experimental models of metastasis. In a panel of human pancreatic cancer samples, expression of ITIH5 correlated with nearly 25% 7-year survival, compared to the 9% 5-year survival for most patients. While this discovery research is in its early stages, ITI5H holds promise for understanding how pancreatic ductal adenocarcinomas metastasize and could be used as a biomarker to guide physicians in planning treatment for patients.
