Pancreatic cancer is one of the most lethal malignancies with few treatment options. Its five-year survival rate is only about 10% in the US. Several treatment options are available for pancreatic cancers, including surgery, chemotherapy, radiation therapy, immunotherapy, and combinational therapies. However, these therapies are ineffective for most patients, and the outcomes are far from satisfactory. Current Immunotherapy Has Limited Effects on Pancreatic Cancer Immunotherapies hold great potential for several types of cancer, but they have limitations to pancreatic cancer. Antibody-based immunotherapy, such as the checkpoint inhibitor drug pembrolizumab, only works for a small portion (1-2%) of pancreatic patients who carry the genomic abnormalities called “mismatch repair-deficient (dMMR) or “microsatellite instability stability high” (MSI-H). T-cell-based immunotherapy, such as Chimeric Antigen Receptor (CAR) T-cell therapy or CAR-T therapy, has shown limited treatment effects on pancreatic cancer because it is difficult for T-cells to penetrate the tumors and kill them. Pancreatic Cancers are Often Called “Cold Tumors” Pancreatic cancers are “cold tumors” or “immune-excluded tumors” because the cancer-killing T-cells couldn’t efficiently infiltrate the tumor and only stay at the margins. Research data shows that pancreatic ductal adenocarcinoma (PDAC) builds up a surrounding microenvironment that suppresses the cancer-killing functions of the immune system. To turn the “cold tumor” into a “hot tumor,” researchers must explore novel approaches to disrupt the tumor-friendly microenvironment around the pancreatic tumors and enable more tumor-killing T-cells to infiltrate the tumor sites. Novel CAR-T Cells May Infiltrate Pancreatic Cancer More Efficiently Avery D. Posey, Jr., Ph.D. at the Center for Cellular Immunotherapy, University of Pennsylvania School of Medicine, is leading a research team to develop a novel type of CAR-T Cell therapy to overcome the limitation of current cell therapy procedures. Unlike antibody drugs, CAR-T therapy uses living cells to treat cancer in three steps. First, doctors collect the cancer-fighting T-cells from patients. Then, specialized technicians will modify those cells in the laboratory with genetic engineering technology. The engineered T-cells will be tailored to attack the patient’s tumor specifically. They are also armed with new genes, enabling them to penetrate tumors more efficiently than the patient’s natural T-cells. As the final step, modified CAR T-cells will be infused back into the patient to let them find and kill the cancer cells. How We Make An Impact With the NFCR’s support, Dr. Posey is collaborating with Dr. Courtney Houchen at the University of Oklahoma Health Sciences Center to conduct the research. They will make the novel CAR-T cells ready for human clinical trials after generating enough data in their laboratories. Learn more about Dr. Posey’s research project on the novel CAR-T Therapy by watching this video. References: CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers. National Cancer Institute, March 10, 2022.