Rapid Generation of TCR and CD8αβ Transgenic Virus Specific T Cells for Immunotherapy of Leukemia.

Details

Serval ID
serval:BIB_0C6CE3A6605F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Rapid Generation of TCR and CD8αβ Transgenic Virus Specific T Cells for Immunotherapy of Leukemia.
Journal
Frontiers in immunology
Author(s)
Bajwa G., Arber C.
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Publication state
Published
Issued date
2022
Peer-reviewed
Oui
Volume
13
Pages
830021
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Virus-specific T cells (VSTs) are an attractive cell therapy platform for the delivery of tumor-targeted transgenic receptors. However, manufacturing with conventional methods may require several weeks and intensive handling. Here we evaluated the feasibility and timelines when combining IFN-γ cytokine capture (CC) with retroviral transduction for the generation of T cell receptor (TCR) and CD8αβ (TCR8) transgenic VSTs to simultaneously target several viral and tumor antigens in a single product.
Healthy donor peripheral blood mononuclear cells were stimulated with cytomegalovirus (CMV) and Epstein-Barr-Virus (EBV) peptide mixtures derived from immunogenic viral proteins, followed by CC bead selection. After 3 days in culture, cells were transduced with a retroviral vector encoding four genes (a survivin-specific αβTCR and CD8αβ). TCR8-transgenic or control VSTs were expanded and characterized for their phenotype, specificity and anti-viral and anti-tumor functions.
CC selected cells were efficiently transduced with TCR8. Average fold expansion was 269-fold in 10 days, and cells contained a high proportion of CD8+ T central memory cells. TCR8+ VSTs simultaneously expressed native anti-viral and transgenic anti-survivin TCRs on their cell surface. Both control and TCR8+ VSTs produced cytokines to and killed viral targets, while tumor targets were only recognized and killed by TCR8+ VSTs.
IFN-γ cytokine capture selects and activates CMV and EBV-specific memory precursor CD8+ T cells that can be efficiently gene-modified by retroviral transduction and rapidly ex vivo expanded. Our multi-specific T cells are polyfunctional and recognize and kill viral and leukemic targets expressing the cognate antigens.
Keywords
CD8 Antigens, Cytokines/metabolism, Cytomegalovirus, Cytomegalovirus Infections/therapy, Herpesvirus 4, Human, Humans, Immunologic Factors, Immunotherapy, Leukemia, Leukocytes, Mononuclear/metabolism, Receptors, Antigen, T-Cell/genetics, cytokine capture, engineered T cells, immunotherapy, interferon-gamma, transgenic CD8, transgenic TCR, virus-specific T cells
Pubmed
Web of science
Open Access
Yes
Create date
31/05/2022 14:09
Last modification date
15/07/2022 6:35
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