Efficacy and safety of novel multifunctional M10 CAR-T cells in HIV-1-infected patients: a phase I, multicenter, single-arm, open-label study

A recent study, published in Cell Discovery, has demonstrated the efficacy and safety of a novel multifunctional M10 CAR-T cell therapy in patients with HIV-1. This phase I, multicenter, single-arm, open-label study performed at Fudan University in China, investigated the therapeutic potential of M10 CAR-T cells. These cells are engineered to possess broad cytotoxic effects on HIV-infected cells, neutralize cell-free viruses, and home towards B-cell follicles through CXCR5 expression. The results showed that 74.3% of the M10 cell infusions led to significant suppression of viral rebound, with viral loads decreasing by an average of 67.1% and sustained reductions in cell-associated HIV-1 RNA levels.

This study aimed to address the persistent challenge of eradicating the HIV-1 viral reservoir, which necessitates lifelong antiretroviral therapy (ART) due to its resistance to conventional treatments. By developing and evaluating multifunctional M10 CAR-T cells, the researchers hypothesize that these engineered cells can effectively target and eliminate HIV-infected cells, including those in latent reservoirs. In total, 18 HIV-1 patients who received two infusions of M10 cells, each followed by two doses of chidamide, a latency-reversing agent were enrolled. The authors found that, on average, M10 CAR-T cells were effective in reducing the size of the HIV-1 viral reservoir. Patients exhibited significant reductions in plasma viral loads and cell-associated HIV-1 RNA levels over the 150-day observation period. Specifically, 10 patients demonstrated a persistent reduction in HIV-1 RNA levels, averaging a decrease of 1.15 log10. The treatment regimen was well tolerated, with no significant adverse effects reported.

These findings highlight the ability of M10 cells to impose selective pressure on the latent viral reservoir, which may contribute to the long-term control of HIV-1. Overall, this study supports the potential of M10 CAR-T cells as a promising therapeutic option for achieving a functional cure for HIV-1/AIDS. The multifunctional design of M10 cells offers a comprehensive approach to eradicating the virus. Therefore, further clinical trials are warranted to confirm the long-term efficacy and safety of M10 CAR-T cell therapy and to explore its potential in combination with other therapeutic strategies.

Reference:

Mao, Y., Liao, Q., Zhu, Y., et al. (2024). Efficacy and safety of novel multifunctional M10 CAR-T cells in HIV-1-infected patients: a phase I, multicenter, single-arm, open-label study. Cell Discovery, 10, 49.

https://doi.org/10.1038/s41421-024-00658-z