The Tumor Infiltrating Lymphocyte (TIL) laboratory is a critical part of new initiative to develop a powerful form of cellular therapy for cancer called “Adoptive T-cell Therapy” (ACT) at MD Anderson. ACT involves the large-scale expansion of TIL (containing T cells) in vitro from tumor specimens followed by infusion of the expanded cells into the patient together with Interleukin-2 (IL-2) as a growth factor. These expanded TIL are infused into cancer patients where they home into and attack tumors. ACT has been shown to be highly successful at eradicating large refractory tumors in greater than 50% of treated melanoma patients at the National Cancer Institute (NCI) in Bethesda, MD.
The goal of the TIL Lab is to develop isolation and expansion methods for TIL and to produce large-scale GMP-grade TIL products for ACT clinical trials for melanoma and other solid tumors. We work closely with MD Anderson’s GMP facility to generate and quality control these large-scale TIL infusion products. In addition, we also work together with pre-clinical researchers in translating new methods and approaches to grow TIL into large-scale GMP grade products for clinical trials.
At present, the TIL Lab is conducting a major Phase II clinical trial with Dr. Patrick Hwu in Stage IV melanoma patients. This clinical trial will treat over 50 patients and is the first time that clinical efficacy of ACT for metastatic melanoma will be independently verified in a large cohort of patients outside of the NCI in Bethesda, MD. In addition to TIL infusion, part of the current Phase II clinical trial is also testing a synergistic therapy by co-infusing melanoma antigen-pulsed autologous dendritic cells together with TIL into patients in order to boost the anti-tumor activity and persistence of the infused T cells.
Future clinical trials testing new approaches at expanding better quality TIL for ACT and modulating TIL activity and survival after infusion are also being planned that will apply the knowledge we gain from our pre-clinical studies. These studies are looking into ways of expanding TIL with a younger and more robust memory T-cell phenotype capable of surviving for longer periods of time after infusion into patients.
We are also developing and testing immunomodulators that activate specific costimulatory pathways in TIL to improve anti-tumor activity and TIL survival after infusion. In addition, we are testing new culture technologies (e.g., different culture vessel configurations and bioreactors) to improve the expansion and quality of TIL products used in ACT. All of this research will be incorporated into future clinical trials aiming to improve the clinical efficacy of ACT.