Today’s antiretroviral therapy (ART) controls HIV infection by preventing HIV from infecting new cells and multiplying within them, but it does not eliminate cells already infected with HIV. Curing people living with HIV has proved challenging because some virus lies dormant within cells and can begin replicating and reinitiate systemic HIV infection once ART is halted.
A research team at Albert Einstein College of Medicine led by Harris Goldstein, M.D., has demonstrated that genetically engineered T cells, dubbed duoCAR-T cells, can effectively target and kill HIV-infected T cells in mice, acting as a functional cure for HIV infection by eliminating these latently infected cells. The study, published online on November 8 in JCI Insight, provides the crucial pre-clinical data that enabled the launch of a phase I/II clinical trial at the University of California-San Francisco and Davis by co-corresponding author, Boro Dropulić, Ph.D., at Caring Cross.
The new duoCAR-T cell therapy involves removing T cells from people with HIV, genetically modifying them to so they will target and destroy HIV-infected cells, and then infusing them back into the people with HIV. In the preclinical studies performed by the Goldstein team, genetically modified human T cells were infused into a “humanized” mouse model of HIV. The T cells localized to the spleen—an important HIV reservoir—where they potently suppressed and eliminated HIV-infected cells without causing observable adverse effects. Other experiments showed that the modified duoCAR-T cells derived from people living with HIV effectively detected and killed human immune cells that had been infected with HIV.
Dr. Goldstein, co-corresponding author on the study, is director of the Einstein-Rockefeller-CUNY Center for AIDS Research, professor of pediatrics and of microbiology & immunology, the Charles Michael Chair in Autoimmune Diseases, and senior associate dean for scientific affairs at Einstein and an allergy & immunology physician at Montefiore Health System. Dr. Dropulić and Kim Anthony-Gonda, Ph.D., the paper’s other two co-corresponding authors, were both previously with Lentigen Technology (a wholly owned subsidiary of Miltenyi Biotec) are currently with Caring Cross, a non-profit organization based in Gaithersburg, MD. Hang Su, Ph.D., a postdoctoral fellow in Dr. Goldstein's lab, was a lead author on the study.
Posted on: Tuesday, November 15, 2022