Pancreatic Cancer (PC) is a highly lethal cancer with the lowest 5-year survival rate due to its aggressiveness and resistance to systemic therapy. PC has the ability to immune escape by mechanisms that include immunosuppression of the dense fibrotic tumor microenvironment and overall low tumor mutational burden. Cellular immunotherapy, involving chimeric antigen receptor (CAR)-T cell, natural killer (NK) cells, and tumor-infiltrating lymphocytes (TILs), has the potential to eliminate cancer cells by restoring cancer immunity. Alfa Oncology is an integrated research, development, and manufacturing organization providing scientific services, primarily ranging from early discovery and development to preclinical research. Here, we are committed to providing a range of cellular immunotherapy development services for PC.
Challenges of cellular immunotherapy for PC
Due to the unique tumor microenvironment (TME) of PC, cellular immunotherapies such as CAR-T therapy are facing more severe challenges. TEM accounts for more than 80% of total pancreatic tumor masses, consisting of the extracellular matrix and numerous types of cellular components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages, dendritic cells, T-cell lymphocytes, and B-cell lymphocytes. CAFs are responsible for the production of extracellular matrix and regulation of tumor behavior. TME immune cells secrete and express molecules that inhibit T-cell activation and limit the anti-tumor response of CAR-T cells. As a result, a physical barrier is formed to prevent the detection, transport and infiltration of engineered immune cells, and this physical barrier has been observed to limit the delivery and activity of chemotherapy.
Fig. 1 Isolation, engineering, and challenges of CAR-T cell therapy in pancreatic adenocarcinoma (PDAC).
PC cellular immunotherapy development services at Alfa Oncology
CAR-T cell therapy generally involves collecting T cells from individuals, genetically engineering them to express a type of CAR-T cell that can recognize and attack cancer cells, and then systematically injecting these cells into the body to exert anti-tumor activity. CAR-T cell therapy is an active, viable, and promising area of research that is still being explored in PC. Our team of experts has years of extensive experience in developing CAR-T therapy for PC. We are able to provide a one-stop solution for CAR-T cells, including antigen identification, CAR-T cell design, isolation, engineering, and expansion.
NK cell therapy is similar to CAR-T cell therapy in that they both transform or enhance immune system cells to effectively fight cancer. Unlike T cells, NK cells can recognize targets in a non-antigen-specific manner without prior sensitization. CAR-NK cells with favorable cytotoxicity, short lifespan, and low manufacturing costs have received much attention as a potential immunotherapeutic tool in the treatment of PC. In addition to providing CAR-T therapy development services, we are also committed to providing CAR-NK therapy development services for PC.
Since TILs come directly from the tumor and already identify many targets on cancer cells, TILs represent an attractive platform for the treatment of PC. Previous studies have demonstrated that TIL infusion is feasible, safe, and clinically active. Tumor-infiltrating lymphocyte (TIL) therapy represents the ultimate personalized therapy, taking advantage of naturally existing tumor-reactive T cells already present within the tumor and then re-infused after in vitro activation and expansion. Alfa Oncology is committed to providing TIL therapy development services for PC, including TIL culture and expansion, PC TIL identification, TIL modification and optimization, and TIL in vitro and in vivo assay.
For more about our services, please contact us. We are glad to work with you!
- Yeo, Dannel, et al. "The next wave of cellular immunotherapies in pancreatic cancer." Molecular Therapy-Oncolytics (2022).
- Akce, Mehmet, et al. "The potential of CAR T cell therapy in pancreatic cancer." Frontiers in immunology 9 (2018): 2166.