Author/Authors :
Ray، نويسنده , , Swagatam and Chhabra، نويسنده , , Arvind and Chakraborty، نويسنده , , Nitya G. and Hegde، نويسنده , , Upendra and Dorsky، نويسنده , , David I. and Chodon، نويسنده , , Thinle and von Euw، نويسنده , , Erika and Comin-Anduix، نويسنده , , Begonya and Koya، نويسنده , , Richard C. and Ribas، نويسنده , , Antoni and Economou، نويسنده , , James S. and Rosenberg، نويسنده , , Steven A. and ، نويسنده ,
Abstract :
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 MIP1ß), 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.
