Journal
JOURNAL OF IMMUNOLOGY
Volume 181, Issue 2, Pages 1063-1070Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.2.1063
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Funding
- NCI NIH HHS [R01 CA088059, R01 CA083130, CA 83130, R01 CA083130-05, CA129816, CA 88059, R01 CA061398-07, R01 CA129816, R01 CA129816-02] Funding Source: Medline
- NCRR NIH HHS [MO1RR06192] Funding Source: Medline
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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 engaging CD4(+) 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 alpha- and beta-chains of a high functional avidity TCR specific for the melanoma epitope, MART-1(27-35) as a prototypic human tumor Ag system. We found that unpolarized CD4(+)CD25(-) T cells engineered to express the MART-1(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(+) CTL. Such TCR engineered CD4(+) T cells, therefore, might be useful in clinical immunotherapy.
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