HIV-specific CAR T cells return to the clinic

Abstract

Over the past decade, chimeric antigen receptor (CAR) T cells have emerged as the prototype gene therapy for B cell leukemias. These so-called living drugs are derived from a patient's own cells, reprogrammed to recognize and destroy cancer cells, and then reintroduced into the body. The huge success of this therapy for cancer is rooted in pioneering clinical and preclinical studies, established more than three decades ago, focused on persistent HIV-1 infection. In this issue of the JCI, Bingfeng Liu et al. revisit HIV-specific CAR T cells in an important clinical study that supports broader application of this groundbreaking therapy. Although curative endpoints were not achieved, these findings lay the foundation for augmented approaches applying combinatorial technologies including antigen supplementation.

Figure 1. CAR T cell function above and below threshold levels of cognate antigen.

Malignant cells, for example CD19⁺ leukemias, express high levels of CD19 antigen at the cell surface and are efficiently killed by CD19 CAR T cells (left). HIV-1–positive cells with latent infection express much lower levels of cell surface antigens (namely, Env), resulting in substantially lower killing efficiencies (middle). An approach to boost HIV-1 CAR T cells with cell-associated Env would provide exogenous antigen in vivo and increase CAR T killing efficiency (right).