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Robust Production of Merkel Cell Polyomavirus Oncogene Specific T Cells From Healthy Donors for Adoptive Transfer.
- Source :
-
Frontiers in immunology [Front Immunol] 2020 Dec 09; Vol. 11, pp. 592721. Date of Electronic Publication: 2020 Dec 09 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- 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 <superscript>+</superscript> 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 <superscript>+</superscript> 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.<br />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.<br /> (Copyright © 2020 Davies, Barrett, Wong, Chang, Muranski and Brownell.)
- Subjects :
- Age Factors
Aged
Antigens, Neoplasm immunology
Biomarkers
Carcinoma, Merkel Cell etiology
Cell Line
Cytokines metabolism
Dendritic Cells immunology
Dendritic Cells metabolism
Epitopes immunology
HLA Antigens
Humans
Immunophenotyping
Middle Aged
Polyomavirus Infections complications
Polyomavirus Infections virology
T-Lymphocytes metabolism
T-Lymphocytes virology
Tissue Donors
Translational Research, Biomedical
Tumor Virus Infections complications
Tumor Virus Infections virology
Adoptive Transfer methods
Carcinoma, Merkel Cell therapy
Merkel cell polyomavirus immunology
Polyomavirus Infections immunology
T-Cell Antigen Receptor Specificity immunology
T-Lymphocytes immunology
Tumor Virus Infections immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 11
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33362774
- Full Text :
- https://doi.org/10.3389/fimmu.2020.592721