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CD4⁺CD25⁻ T Cells Transduced to Express MHC Class I-Restricted Epitope-Specific TCR Synthesize Th1 Cytokines and Exhibit MHC Class I-Restricted Cytolytic Effector Function in a Human Melanoma Model

Chhabra, Arvind and Yang, Lili and Wang, Pin and Comin-Anduix, Begoña and Das, Raja and Chakraborty, Nitya G. and Ray, Swagatam and Mehrotra, Shikhar and Yang, Haiguang and Hardee, Cinnamon L. and Hollis, Roger and Dorsky, David I. and Koya, Richard and Kohn, Donald B. and Ribas, Antoni and Economou, James S. and Baltimore, David and Mukherji, Bijay (2008) CD4⁺CD25⁻ T Cells Transduced to Express MHC Class I-Restricted Epitope-Specific TCR Synthesize Th1 Cytokines and Exhibit MHC Class I-Restricted Cytolytic Effector Function in a Human Melanoma Model. Journal of Immunology, 181 (2). pp. 1063-1070. ISSN 0022-1767. PMCID PMC2715965. https://resolver.caltech.edu/CaltechAUTHORS:20200417-142716754

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Abstract

Cytolytic T cell-centric active specific and adoptive immunotherapeutic approaches might benefit from the simultaneous engagement of CD4⁺ T cells. Considering the difficulties in simultaneously engagingCD4⁺ and CD8⁺ T cells in tumor immunotherapy, especially in an Ag-specific manner, redirecting CD4⁺ T cells to MHC class I-restricted epitopes through engineered expression of MHC class I-restricted epitope-specific TCRs in CD4⁺ T cells has emerged as a strategic consideration. Such TCR-engineered CD4⁺ T cells have been shown to be capable of synthesizing cytokines as well as lysing target cells. We have conducted a critical examination of functional characteristics of CD4⁺ T cells engineered to express the α- and β-chains of a high functional avidity TCR specific for the melanoma epitope, MART-1, as a prototypic human tumor Ag system. We found that unpolarized CD4⁺CD25⁻ T cells engineered to express the MART-1 TCR selectively synthesize Th1 cytokines and exhibit a potent Ag-specific lytic granule exocytosis-mediated cytolytic effector function of comparable efficacy to that of CD8⁺ CTL. Such TCR engineered CD4⁺ T cells, therefore, might be useful in clinical immunotherapy.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.4049/jimmunol.181.2.1063DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715965/PubMed CentralArticle
ORCID:
AuthorORCID
Baltimore, David0000-0001-8723-8190
Additional Information:© 2008 by The American Association of Immunologists. Received January 31, 2008. Accepted May 15, 2008. Published online July 7, 2008. This work was supported by Public Health Service Grants CA 83130 (to B.M.), CA 88059 (to B.M.), CA129816 (to J.S.E.), grants from the Dowling Foundation (to B.M.), General Clinical Research Grant MO1RR06192 (to University of Connecticut Health Center), Samuel Waxman Foundation, and WM Keck Foundation (to J.S.E. for UCLA-CALTECH-CHLA-USC-UCONN Consortium on Translational Program in Engineered Immunity). The authors have no financial conflict of interest. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Funders:
Funding AgencyGrant Number
NIHCA 83130
NIHCA 88059
NIHCA129816
Dowling FoundationUNSPECIFIED
NIHMO1RR06192
Samuel Waxman FoundationUNSPECIFIED
W. M. Keck FoundationUNSPECIFIED
Issue or Number:2
PubMed Central ID:PMC2715965
Record Number:CaltechAUTHORS:20200417-142716754
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200417-142716754
Official Citation:CD4+CD25− T Cells Transduced to Express MHC Class I-Restricted Epitope-Specific TCR Synthesize Th1 Cytokines and Exhibit MHC Class I-Restricted Cytolytic Effector Function in a Human Melanoma Model Arvind Chhabra, Lili Yang, Pin Wang, Begoña Comin-Anduix, Raja Das, Nitya G. Chakraborty, Swagatam Ray, Shikhar Mehrotra, Haiguang Yang, Cinnamon L. Hardee, Roger Hollis, David I. Dorsky, Richard Koya, Donald B. Kohn, Antoni Ribas, James S. Economou, David Baltimore, Bijay Mukherji The Journal of Immunology July 15, 2008, 181 (2) 1063-1070; DOI: 10.4049/jimmunol.181.2.1063
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102619
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:20 Apr 2020 14:05
Last Modified:20 Apr 2020 14:05

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