Medscape: Triple cytokine scaffold builds long-lived CAR T cells against HIV

Medscape news story

For 25 years, researchers have engineered immune cells to hunt down HIV. The approach, known as chimeric antigen receptor (CAR) T-cell therapy, extracts a patient’s T cells, engineers them to recognize a specific target on infected cells, and infuses them back into the patient. The engineered cells circulate, find their target, and kill. In fact, the challenge has never actually been about whether a target could be killed; it lies in getting the newly engineered cells to last long enough to finish the job.

The first generation of anti-HIV CAR T cells, developed in the late 1990s, showed only modest efficacy against the virus in early clinical trials. Later designs improved: multispecific targeting domains, costimulatory signaling architectures, and constructs engineered to resist viral escape.

To date, none of the tested anti-HIV CAR T cells have prevented viral rebound after antiretroviral therapy (ART) is discontinued. A 2021 phase 1 trial of CAR T cells targeting HIV after interruption of ART saw all six participants rebound at a median of just over 5 weeks.

A growing number of research groups have begun to question whether the problem was never the weapon but the forge. Now, a study published in Science Advances, takes the idea further than anyone else.

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