Robust Production of Merkel Cell Polyomavirus Oncogene Specific T Cells From Healthy Donors for Adoptive Transfer.

Autor:	Davies SI; Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, United States.; Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC, United States.; Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, MD, United States., Barrett J; Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, United States., Wong S; Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, United States., Chang MJ; Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, United States., Muranski PJ; Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, United States.; Columbia Center for Translational Immunology (CCTI), Cellular Immunotherapy Laboratory, Columbia University Medical Center, New York City, NY, United States., Brownell I; Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2020 Dec 09; Vol. 11, pp. 592721. Date of Electronic Publication: 2020 Dec 09 (Print Publication: 2020).
DOI:	10.3389/fimmu.2020.592721
Abstrakt:	Virus positive Merkel cell carcinoma (VP-MCC) is an aggressive but immunogenic skin malignancy driven by Merkel cell polyomavirus (MCPyV) T antigen (TAg). Since adoptive T cell transfer (ACT) can be effective against virus-driven malignancies, we set out to develop a methodology for generating MCPyV TAg specific T cells. MCPyV is a common, asymptomatic infection and virus-exposed healthy donors represent a potential source of MCPyV TAg specific T cells for ACT. Virus specific T cells were generated using monocyte-derived dendritic cells (moDCs) pulsed with MCPyV TAg peptide libraries and co-cultured with autologous T cells in supplemented with pro-inflammatory and homeostatic cytokines for 14 days. Specific reactivity was observed predominantly within the CD4 + T cell compartment in the cultures generated from 21/46 random healthy donors. Notably, responses were more often seen in donors aged 50 years and older. TAg specific CD4 + T cells specifically secreted Th1 cytokines and upregulated CD137 upon challenge with MCPyV TAg peptide libraries and autologous transduced antigen presenting cells. Expanded T cells from healthy donors recognized epitopes of both TAg splice variants found in VP-MCC tumors, and minimally expressed exhaustion markers. Our data show that MCPyV specific T cells can be expanded from healthy donors using methods appropriate for the manufacture of clinical grade ACT products. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2020 Davies, Barrett, Wong, Chang, Muranski and Brownell.)
Databáze:	MEDLINE
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