TY - JOUR
T1 - MHC-I-restricted melanoma antigen specific TCR-engineered human CD4+ T cells exhibit multifunctional effector and helper responses, in vitro
AU - Ray, Swagatam
AU - Chhabra, Arvind
AU - Chakraborty, Nitya G.
AU - Hegde, Upendra
AU - Dorsky, David I.
AU - Chodon, Thinle
AU - von Euw, Erika
AU - Comin-Anduix, Begonya
AU - Koya, Richard C.
AU - Ribas, Antoni
AU - Economou, James S.
AU - Rosenberg, Steven A.
AU - Mukherji, Bijay
N1 - Funding Information:
The work was supported by PHS grants CA 83130 (BM), CA 88059 (BM), and CA 129816 (JSE) and grants from the Dowling Foundation (BM), Samuel Waxman Cancer Research Foundation , W.M. Keck Foundation , Joy and Jerry Monkarsh Fund (JSE for UCLA-CALTECH-CHLA-USC-UCONN Consortium on Translational Program in Engineered Immunity), Breast Cancer Alliance, Connecticut (AC) and MO 1RR06192 from GCRC, UCHC .
PY - 2010/9
Y1 - 2010/9
N2 - MHC class I-restricted human melanoma epitope MART-127-35 specific TCR-engineered CD4+CD25- T cells synthesize Th1 type cytokines and exhibit cytolytic effector function upon cognate stimulation. A detailed characterization of such TCR-engineered CD4+CD25- T cells now reveals that they are multifunctional. For example, they undergo multiple rounds of division, synthesize cytokines (IFN-γ, TNF-α, IL-2, and MIP1β), lyse target cells, and "help" the expansion of the MART-127-35 specific CD8+ T cells when stimulated by the MART-127-35 peptide pulsed DC. Multiparametric analyses reveal that a single TCR-engineered CD4+ T cell can perform as many as five different functions. Nearly 100% MART-127-35 specific TCR expressing CD4+ T cells can be generated through retroviral vector-based transduction and one round of in vitro stimulation by the peptide pulsed DC. MHC class I-restricted tumor epitope specific TCR transduced CD4+ T cells, therefore, could be useful in immunotherapeutic strategies for melanoma or other human malignancies.
AB - MHC class I-restricted human melanoma epitope MART-127-35 specific TCR-engineered CD4+CD25- T cells synthesize Th1 type cytokines and exhibit cytolytic effector function upon cognate stimulation. A detailed characterization of such TCR-engineered CD4+CD25- T cells now reveals that they are multifunctional. For example, they undergo multiple rounds of division, synthesize cytokines (IFN-γ, TNF-α, IL-2, and MIP1β), lyse target cells, and "help" the expansion of the MART-127-35 specific CD8+ T cells when stimulated by the MART-127-35 peptide pulsed DC. Multiparametric analyses reveal that a single TCR-engineered CD4+ T cell can perform as many as five different functions. Nearly 100% MART-127-35 specific TCR expressing CD4+ T cells can be generated through retroviral vector-based transduction and one round of in vitro stimulation by the peptide pulsed DC. MHC class I-restricted tumor epitope specific TCR transduced CD4+ T cells, therefore, could be useful in immunotherapeutic strategies for melanoma or other human malignancies.
KW - Cancer immunotherapy
KW - Multi functional CD4 T cells
KW - TCR
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U2 - 10.1016/j.clim.2010.04.013
DO - 10.1016/j.clim.2010.04.013
M3 - Article
C2 - 20547105
AN - SCOPUS:77955270629
SN - 1521-6616
VL - 136
SP - 338
EP - 347
JO - Clinical Immunology
JF - Clinical Immunology
IS - 3
ER -