Arvind Chhabra
University of Connecticut Health Center, USA
Title: Engineering customized anti-tumor immune response: Biology of MHC class I restricted TCR engineered CD4 T cells
Biography
Biography: Arvind Chhabra
Abstract
TCR engineered anti-tumor T cells have produced remarkable responses in cancer patients, however, generation of customized anti-tumor T cells with predefined functional characteristics remains a challenge. We are working on characterizing the biology of tumor antigen specific TCR engineered T cells, to develop methodologies for generating T cells with predefined functional profiles. We have recently shown that TCR engineering approach can also be utilized to program human CD4 T cells to function as MHC class I restricted anti-tumor effectors that can simultaneously exhibit a helper response as well as cytolytic effector response (Chhabra et al., JI, 2008 and Ray et al., J. Clin. Immunol., 2010). Interestingly, we have found that these MHC class I restricted multifunctional CD4 T cells can also mitigate regulatory T cell (Treg) mediated immune suppression. Furthermore, we have found that these engineered CD4 T cells are also susceptible to epitope specific activation induced cell death (AICD), that has distinct differences from AICD in TCR engineered CD8 T cells (Chhabra et al., JI, 2013). We will share our recent findings on biology of MHC class I restricted CD4 T cells, such as their effector function profile, ability to mitigate Treg-mediated immune suppression, and their susceptibility to undergo AICD. We will also discuss molecular pathways involved in development of multifunctional effector profile of MHC class I restricted CD4 T cells, and strategies for generating customized anti-tumor T cells with predefined functional profiles.
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