Recent advances in CD8+ T cell-based immune therapies for HIV cure

Abstract

Achieving a cure for HIV infection is a global priority. There is substantial evidence supporting a central role for CD8⁺ T cells in the natural control of HIV, suggesting the rationale that these cells may be exploited to achieve remission or cure of this infection. In this work, we review the major challenges for achieving an HIV cure, the models of HIV remission, and the mechanisms of HIV control mediated by CD8⁺ T cells. In addition, we discuss strategies based on this cell population that could be used in the search for an HIV cure. Finally, we analyze the current challenges and perspectives to translate this basic knowledge toward scalable HIV cure strategies.

Keywords: CD8+ T cells; Cure; HIV; Immunotherapy; Remission.

Fig. 1

CD8⁺T cell-based immunotherapeutic strategies for HIV cure. Various strategies seek to enhance the number and functional attributes of CD8⁺ T cells to favor viral control and can be divided into injected compounds and adoptive therapies. Injected compounds include i) vaccination and broadly neutralizing antibodies to promote endogenous CD8⁺ T cell responses, ii) γ-chain cytokines such as IL-15 and superagonists, which expand them and promote their cytotoxic capacity, and iii) combinatorial immune checkpoint blockade. For adoptive therapies, autologous CD8⁺ T cells could be isolated for cognate in vitro stimulation with HIV peptides to expand virus-specific cells, or for gene modification to generate CAR T cells. Chemokine receptors, such as CXCR5, could also be inserted into the genome of engineered cells to promote migration into lymphoid follicles. Expanded autologous HIV-specific cells or CAR T cells could be further reprogrammed with GSK3 inhibitors to promote TCF-1 expression and stemness, which may contribute to long-lived memory responses. Finally, in vitro-manipulated cells can be reinfused into the individual.