Isolation of CD4+ T cells specific for neoantigens created by recurrent driver mutations in non-small cell lung cancer (NSCLC) and melanoma.

12054Background: T cells specific for neoantigens encoded by mutated genes are increasingly recognized as mediators of tumor destruction after immune checkpoint inhibitor therapy or adoptive cell transfer. Unfortunately, almost all neoantigens result from random mutations that are patient-specific. Here, we describe CD4+ T cell responses one melanoma patient and two NSCLC patients that are specific for recurrent driver mutations in their cancers. Methods: Neoantigen-reactive T cells were expanded and cloned by peptide stimulation of the peripheral blood from cancer patients. Results: The melanoma patient had a CD4+ T cell response to the peptide encoded by the BRAF V600E mutation found in 40% of melanoma, and obtained a complete response following adoptive transfer of tumor infiltrating lymphocytes (TIL). The BRAF V600E specific cells showed a Th1 memory phenotype, were preferentially localized to the tumor at the time of resection, and expanded and persisted in blood greater than 2 years after TIL therap...