While lifelong antiretroviral therapy (ART) suppresses HIV replication, it does not eliminate the infection. Researchers led by Harris Goldstein, M.D., and Steven Almo, Ph.D., demonstrated that bespoke proteins, termed Immuno-STATs, developed by the Almo lab can selectively induce a potent immune responses against HIV-infected cells or cancer cells that were far more focused than those induced by vaccines. The results were published online on August 5 in the Journal of Virology.

April Mueller, an MSTP student in the Goldstein lab, demonstrated that Immuno-STATs can stimulate highly focused HIV epitope-specific T-cell responses capable of targeting the “Achilles heel” of the virus. The protein works by delivering two key signals to T cells: a peptide-specific signal through their T-cell receptors and another through CD28, a T-cell molecule required to activate “naïve” T cells. This scalable strategy generated large numbers of HIV-specific T cells from white blood cells from people not previously exposed to HIV, which were highly effective at killing HIV-infected cells. The strategy also worked against cells carrying a melanoma-related protein, showing its potential use for cancer immunotherapy.

The work should enhance the therapeutic effectiveness of adoptive transfer of HIV-specific T cells isolated from patients and reinfused after selective Immuno-STAT-driven expansion of T cells providing the optimal targeting of HIV-infected cells. This same strategy may be effective for other viruses as well as many cancers.

Dr. Goldstein is professor of pediatrics and microbiology & immunology, senior associate dean for scientific affairs, the Charles Michael Chair in Autoimmune Diseases, and director of the Einstein-Rockefeller-CUNY Center for AIDS Research. Dr. Almo is professor and chair of biochemistry, the Wollowick Family Foundation Chair in Multiple Sclerosis and Immunology, director of the Macromolecular Therapeutics Developmental Facility, co-leader of the Cancer Therapeutics Program at the National Cancer Institute-designated Montefiore Einstein Comprehensive Cancer Center and co-founder of Cue Biopharma, a clinical stage oncology company that licensed the Immuno-STAT platform as its foundational technology.