Abstract
Abstract
Durable complete response rates of 20% have been observed in clinical trials of patients with metastatic melanoma employing adoptive cell transfer (ACT) of patient derived tumor infiltrating lymphocytes (TIL). Here we provide a detailed analysis of the response of TIL administered to a patient with metastatic melanoma who exhibited a complete response ongoing greater than 3 years. Using whole-exome and RNA-Seq sequencing and bioinformatic analysis of the patient's matched tumor and normal gDNA we identified over 4,000 non-synonymous somatic mutation variants. We screened 745 somatically mutated genes using tandem minigene constructs expressing transcripts expressed in autologous tumor cells whose expression levels were greater than 0.1% of the levels of beta actin. These tandem minigenes were then transfected into autologous B cells and then analyzed for their ability to stimulate the administered T cells. Our results indicated that the autologous TIL distinctly recognized 10 somatically mutated gene products, each of which was recognized in the context of three different HLA class I restriction elements expressed by the patient's tumor. Detailed T cell clonal analysis revealed that 9 of the top 20 most prevalent clones present in the infused TIL, comprised over ¼ of total infused cells and recognized mutated antigens. These results further supported our efforts to identify and enrich mutation-reactive T cells for the treatment of patients with metastatic cancer.
Citation Format: Todd D. Prickett, Jessica Crystal, Jared Gartner, Xin Yao, Anna Pasetto, Alena Gros, Yong-Chen Lu, Yong F. Li, Mona El-Gamil, Steven A. Rosenberg, Paul Robbins. Durable complete response in a patient with metastatic melanoma following adoptive transfer of autologous T cells recognizing 10 mutated tumor antigens. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr PR002.