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.
How can TILs be used for PC treatment?
The tumor microenvironment (TME) in PC accounts for more than 80% of total pancreatic tumor masses, consisting of cellular and stromal components. Among multiple types of cellular components, cancer-associated fibroblasts (CAFs) play a dominant role in the PC stroma, interacting with PC cells and having a critical impact on patient survival. CAFs reduce PC perfusion by producing large amounts of peritumoral stroma and are thought to contribute to severe PC drug resistance. Therefore, the TME of PDAC is essentially immunosuppressive. Multiple mechanisms help PC cells to evade the antitumor immune response consisting of tumor-infiltrating leukocytes, especially TILs, M2 macrophages, TINs, and myeloid-derived suppressor cells. Among those tumor-infiltrating immune cells, TILs refer to all lymphocytic cell populations that have invaded the tumor tissue. In addition to quantification of response to PC subclassification, the ability of TILs to identify and kill cancer cells is attractive for the treatment of PC.
Service offering
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. To achieve TIL treatment, the TME of cancer must be overcome and cancer cells must be effectively eliminated. Currently, there are two main approaches to help establish TIL therapy, including extending TILs and engineering TILs. Our team of experts has years of extensive experience in developing cellular immunotherapy for PC. Based on our state-of-the-art platforms and technologies, we are committed to helping our customers develop TIL therapy for PC.
- TIL culture and expansion
By expanding the TILs, a larger army of immune cells can be obtained that have been trained to recognize and attack the patient's PC. Strategic options for improving TIL production and PC tumor responsiveness:
-PD-1 blockade
-4-1BB stimulation
-CD8+ T cell enrichment
- PC TIL identification
-Measurement of T cell phenotype, activation markers, and reactivity
- TIL modification and optimization
Engineering TILs can enhance their ability to fight cancer cells. Genetic modification of TILs can make them resistant to tumor signaling, which normally shuts down T cells.
- TIL in vitro assay
-Efficacy test of TILs
-Cytotoxicity test against target PC cells
- TIL preclinical in vivo assay
-Multiple PC-related preclinical models available for in vivo experiments
-Efficacy test of TILs
-Viability and bio-distribution study of TILs
-Toxicity evaluation of TILs
TIL therapy is dependent upon both the quantity and quality of the lymphocytes recovered from the original source.
TIL treatment depends primarily on the quantity and quality of lymphocytes recovered from the original source. Our team of experts is committed to advancing our clients' projects with high-quality, cost-effective services. For more about our services, please contact us.
Reference
- Yeo, Dannel, et al. "The next wave of cellular immunotherapies in pancreatic cancer." Molecular Therapy-Oncolytics (2022).