# Allogeneic cytotoxic gammadelta T cells for HIV cure immunotherapy > **NIH NIH R21** · GEORGE WASHINGTON UNIVERSITY · 2021 · $234,403 ## Abstract Allogeneic cytotoxic γδ T cells for HIV cure immunotherapy PROJECT SUMMARY HIV Cure strategies based on the “shock and kill” approach require the use of compounds to reactivate HIV from latency and potent immune responses to eliminate HIV-infected cells. Efforts have mostly focused on enhancing HIV-specific CD8 T cell responses but have faced a number of limitations including viral escape, immune exhaustion and inaccessibility to the B cell follicle. γδ T cells, specially the most abundant peripheral blood population, Vδ2 cells, constitute an attractive alternative cytotoxic cell population with unique properties largely exploited in adoptive cell therapies for different malignancies that we have started to explore for HIV cure purposes. In our previous studies, we showed that autologous Vδ2 γδ T cells from people living with HIV (PLWH) ART- suppressed are particularly effective inhibiting HIV replication and the first evidence that expanded Vδ2 cells target and eliminate HIV-infected resting CD4 T (rCD4) T cells after latency reversal. These studies constitute the basis for further investigation towards translating this alternative approach into the clinic. Vδ2 cells recognize intermediates of the mevalonate pathway in an MHC-unrestricted fashion. They respond to a given challenge by both up and/or downregulating specific receptors depending on the infectious/malignant environment displaying a unique functional plasticity that enables them i) to exert direct cytotoxicity and ii) to initiate and boost adaptive immune responses. Vδ2 cell phenotype can be shaped by ex vivo manipulating the mevalonate pathway using Aminobisphosphonates (nBPs) and IL-2 or IL-15 leading to Vδ2 cell activation and expansion. Similarly, to NK cells, combination of IL-2 and IL-15 with other cytokines and factors may favor the development of an effector memory phenotype with enhanced cytolytic activity against HIV-infected cells. Additionally, the lack of MHC restriction would allow for an allogeneic adoptive γδ T cell immunotherapy, that would be required for HIV cure since Vδ2 cells are targets of HIV infection. Allogeneic adoptive cell transfer has been explored in the cancer field and merits further investigation for HIV cure. Exploiting these unique features would allow the generation of a cytotoxic effector population with phenotypic and functional properties suited for targeting reactivated HIV- infected cells. Given Vδ2 cell functional plasticity, we hypothesize that manipulation of the mevalonate pathway and proper cytokine combinations will allow generation of a universal cytotoxic effector cell product of ex vivo expanded allogeneic Vδ2 cells that will recognize and kill HIV-infected cells upon latency reversal. These hypotheses will be addressed in the experiments of the following Specific Aims: (1) to determine whether allogeneic expanded Vδ2 cells efficiently target and eliminate HIV-infected cells upon latency reversal and (2) to explore conditions to devel... ## Key facts - **NIH application ID:** 10256995 - **Project number:** 1R21AI157864-01A1 - **Recipient organization:** GEORGE WASHINGTON UNIVERSITY - **Principal Investigator:** Natalia Soriano-Sarabia - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $234,403 - **Award type:** 1 - **Project period:** 2021-04-06 → 2023-03-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10256995 ## Citation > US National Institutes of Health, RePORTER application 10256995, Allogeneic cytotoxic gammadelta T cells for HIV cure immunotherapy (1R21AI157864-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10256995. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*