CD4 super(+)CD25 super(-) 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

• Published in: The Journal of immunology (1950) 2008-07, Vol.181 (2), p.1063-1070
• Main Authors: Chhabra, Arvind, Yang, Lili, Wang, Pin, Comin-Anduix, Begona, Das, Raja, Chakraborty, Nitya G, Ray, Swagatam, Mehrotra, Shikhar, Yang, Haiguang, Hardee, Cinnamon L, Hollis, Roger, Dorsky, David I, Koya, Richard, Kohn, Donald B, Ribas, Antoni, Economou, James S, Baltimore, David, Mukherji, Bijay
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606

Cytolytic T cell-centric active specific and adoptive immunotherapeutic approaches might benefit from the simultaneous engagement of CD4 super(+) T cells. Considering the difficulties in simultaneously engaging CD4 super(+) and CD8 super(+) T cells in tumor immunotherapy, especially in an Ag-specific manner, redirecting CD4 super(+) T cells to MHC class I-restricted epitopes through engineered expression of MHC class I-restricted epitope-specific TCRs in CD4 super(+) T cells has emerged as a strategic consideration. Such TCR-engineered CD4 super(+) 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 super(+) T cells engineered to express the alpha - and beta -chains of a high functional avidity TCR specific for the melanoma epitope, MART-1 sub(27-35), as a prototypic human tumor Ag system. We found that unpolarized CD4 super(+)CD25 super(-) T cells engineered to express the MART-1 sub(27-35) 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 super(+) CTL. Such TCR engineered CD4 super(+) T cells, therefore, might be useful in clinical immunotherapy.