Recapitulating the qualities of HIV-specific CD8 + T cells from spontaneous controllers

Studies in spontaneous controllers of HIV and, more recently, post-treatment controllers have shown that effective HIV-specific CD8 + T cell responses may mediate control of the virus in the absence of antiretroviral therapy. The purpose of this review is to first discuss the unique features of HIV-specific CD8 + T cells in spontaneous controllers. We will then explore how qualities of these cells might be harnessed using T cell engineering strategies.

Several recent studies have deepened our understanding of HIV-specific CD8 + T cell responses in spontaneous controllers. These have included studies elucidating mechanisms by which preferential antigen restriction, specificity, sensitivity, and breadth promote enhanced T cell responses in spontaneous controllers, as well as studies demonstrating that manipulating the differentiation state or localization of HIV-specific T cells might alter their ability to control the virus. In parallel, many recently-developed approaches to engineer anti-cancer T cells could be used to recapitulate key properties of HIV-specific CD8 + T cells from spontaneous controllers (e.g., sensitive antigen receptors, targeted recognition of evolutionarily conserved and/or mutationally constrained epitopes, T cell stem/memory-like functional capacity).

We identify several opportunities to apply novel approaches being developed in immuno-oncology to enhance the function of engineered T cells for HIV.