Targeting Tumor Neoantigen-specific Tumor Infiltrating Lymphocytes in Non-small Cell Lung Cancer

JI Program: Pulmonary


Tumor infiltrating lymphocytes (TILs) comprise a subset of white blood cells isolated from the tumor and surrounding parenchyma that are thought to mediate tumor-specific immune responses. Autologous TIL cultures, isolated from resected tumor tissue, expanded ex vivo and subsequently reinfused into the preconditioned donor patient, have been shown to elicit durable response rates with some instances of long-term survival. In contrast, another subset of TILs appears to attenuate clinical response. We hypothesize that TILs which recognize tumor-specific neoantigens originate from somatic mutations and are more effective in eliciting a clinically significant response. As proof of concept, it has been shown that TILs harvested from resected metastatic lung tumors from a subject with metastatic colorectal carcinoma recognized neoantigens generated by the mutant KRAS-G12D. Re-infusion of expanded TILs led to a significant antitumor response in this subject. The aim of our study is to utilize high throughput sequencing and tetramer flow cytometry to identify tumor-specific neoantigens derived from patients with non-small cell lung carcinoma, both adenocarcinomas and squamous cell carcinomas, as a prelude to the treatment of NSCLC patients with autologous T cells.