MHC-I-restricted melanoma antigen specific TCR-engineered human CD4+ T cells exhibit multifunctional effector and helper responses, in vitro

Swagatam Ray, Arvind Chhabra, Nitya G. Chakraborty, Upendra Hegde, David I. Dorsky, Thinle Chodon, Erika von Euw, Begonya Comin-Anduix, Richard C. Koya, Antoni Ribas, James S. Economou, Steven A. Rosenberg, Bijay Mukherji

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)338-347
Number of pages10
JournalClinical Immunology
Volume136
Issue number3
DOIs
StatePublished - Sep 1 2010

Keywords

  • Cancer immunotherapy
  • Multi functional CD4 T cells
  • TCR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Ray, S., Chhabra, A., Chakraborty, N. G., Hegde, U., Dorsky, D. I., Chodon, T., von Euw, E., Comin-Anduix, B., Koya, R. C., Ribas, A., Economou, J. S., Rosenberg, S. A., & Mukherji, B. (2010). MHC-I-restricted melanoma antigen specific TCR-engineered human CD4+ T cells exhibit multifunctional effector and helper responses, in vitro. Clinical Immunology, 136(3), 338-347. https://doi.org/10.1016/j.clim.2010.04.013