Development of genetically engineered TCR-transduced T cells for immunotherapy of chronic HBV and HCV infections

Tuesday, October 09, 2012 — Poster Session I
1:00 p.m. – 3:00 p.m	Natcher Conference Center, Building 45	NIDDK	INFECTDIS-3

Authors

• S Park
• H Park
• W Pan
• B Rehermann

Abstract

A vigorous CD8 T cell response is required to spontaneously clear HBV and HCV. However, in chronic HBV and HCV infection, the function of virus-specific T cells is impaired. Here, we set out to use adoptive T cell therapy with TCR-engineered lymphocytes to restore HBV- and HCV-specific immune responses in chronic infection. We identified MHC class I-restricted HBV and HCV-specific T cell receptors (TCRs) with high anti-viral activity from subjects who mounted successful T cell responses and cleared acute viral infections. These TCRs were cloned into retroviral vectors and re-expressed in lymphocytes of chimpanzees with chronic HBV and HCV infection. The transduced T cells gained a broad spectrum of antigen-specific effector functions (IFN-g secretion, cytotoxicity and proliferation). The TCR-transduced T cells were expanded to high numbers with anti-CD3 plus IL-21/IL-15 stimulation, which resulted in a preservation of their differentiation status and a lower frequency of immunosuppressive Tregs. Collectively, our results demonstrate that the TCR gene transfer can efficiently redirect the antigen specificity of resting T cells and generate a large number of functional effector T cells. These expanded effector T cells will be used in adoptive immunotherapy to restore therapeutic immune responses of chimpanzees with chronic HBV- and HCV infection.

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