American Association for Cancer Research
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Supplementary Figure 1 from Durable Complete Response from Metastatic Melanoma after Transfer of Autologous T Cells Recognizing 10 Mutated Tumor Antigens

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posted on 2023-04-03, 23:03 authored by Todd D. Prickett, Jessica S. Crystal, Cyrille J. Cohen, Anna Pasetto, Maria R. Parkhurst, Jared J. Gartner, Xin Yao, Rong Wang, Alena Gros, Yong F. Li, Mona El-Gamil, Kasia Trebska-McGowan, Steven A. Rosenberg, Paul F. Robbins

The number of each of the six classes of base substitutions resulting in non-synonymous changes in the whole exome screen is shown.

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Adelson Medical Research Foundation

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ARTICLE ABSTRACT

Immunotherapy treatment of patients with metastatic cancer has assumed a prominent role in the clinic. Durable complete response rates of 20% to 25% are achieved in patients with metastatic melanoma following adoptive cell transfer of T cells derived from metastatic lesions, responses that appear in some patients to be mediated by T cells that predominantly recognize mutated antigens. Here, we provide a detailed analysis of the reactivity of T cells administered to a patient with metastatic melanoma who exhibited a complete response for over 3 years after treatment. Over 4,000 nonsynonymous somatic mutations were identified by whole-exome sequence analysis of the patient's autologous normal and tumor cell DNA. Autologous B cells transfected with 720 mutated minigenes corresponding to the most highly expressed tumor cell transcripts were then analyzed for their ability to stimulate the administered T cells. Autologous tumor-infiltrating lymphocytes recognized 10 distinct mutated gene products, but not the corresponding wild-type products, each of which was recognized in the context of one of three different MHC class I restriction elements expressed by the patient. Detailed clonal analysis revealed that 9 of the top 20 most prevalent clones present in the infused T cells, comprising approximately 24% of the total cells, recognized mutated antigens. Thus, we have identified and enriched mutation-reactive T cells and suggest that such analyses may lead to the development of more effective therapies for the treatment of patients with metastatic cancer. Cancer Immunol Res; 4(8); 669–78. ©2016 AACR.

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