Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer

Hotspot KRAS mutations exist in various cancers, especially pancreatic, lung and colorectal cancer. Mutations in KRAS are implicated in the development of pancreatic cancer and are associated with poor prognosis of the patients. KRAS is an attractive target for cancer treatment because it is a driver mutation and is likely expressed by all cells in a tumor. Recently,T cells targeting mutant KRAS have been identified in patients with epithelial cancers, and these T-cell receptors (TCR) have been characterized. For example, TCRs that target mutant KRAS G12D peptides presented by HLA-C\*08:02, and a TCR that targets a KRAS G12V peptide presented by HLA-A\*11:01 have been identified. Mutant KRAS-reactive T cells appear capable of inducing tumor regression as highlighted in a patient with metastatic colorectal cancer who experienced regression of metastatic tumors after infusion of HLA-C\*08:02-restricted KRAS-G12D reactive tumor-infiltrating lymphocytes (TIL). The investigators will test the safety and activity of adoptive transfer of autologous T cells genetically engineered to express a TCR that targets mutant KRAS G12V in the context of HLA-A\*11:01 in HLA-matched patients with advanced pancreatic cancer that express mutant KRAS G12V. The investigators will also measure the in vivo survival of engineered T cells.