Journal
CLINICAL IMMUNOLOGY
Volume 136, Issue 3, Pages 338-347Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2010.04.013
Keywords
Cancer immunotherapy; TCR; Multi functional CD4 T cells
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Funding
- PHS [CA 83130, CA 88059, CA 129816]
- Dowling Foundation
- Samuel Waxman Cancer Research Foundation
- W.M. Keck Foundation
- Joy and Jerry Monkarsh Fund
- Breast Cancer Alliance
- Connecticut
- GCRC, UCHC [MO 1RR06192]
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MHC class I-restricted human melanoma epitope MART-1(27-35) 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-gamma, TNF-alpha, IL-2, and MIP1 beta), lyse target cells, and help the expansion of the MART-1(27-35) specific CD8+ T cells when stimulated by the MART-1(27-35) 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-1(27-35) 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. (C) 2010 Elsevier Inc. All rights reserved.
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