# Proof of concept studies for in vivo produced CAR-T cells that target B cell follicles as a treatment for HIV > **NIH NIH R41** · MARPAM PHARMA, LLC · 2024 · $302,248 ## Abstract ABSTRACT MarPam Pharma is developing a chimeric antigen receptor (CAR)-T cell treatment that targets viral reservoirs for durable remission of HIV without the need for antiretroviral therapies (ART). This treatment is an HIV-specific CAR (specifically, CD4-MBL-CAR) T cell therapy that employs the CXCR5 chemokine receptor as a homing device to direct anti-HIV killer T cells into “hidden” viral reservoirs in B cell follicles of secondary lymphoid tissue, so that they can kill HIV-producing cells where the majority of viral replication occurs. Using the best in vivo nonhuman primate (NHP) model of HIV, we developed CAR/CXCR5-T cells that show successful homing to B cell follicles, evidence of direct contact with viral RNA+ infected cells, markedly decreased virus in B cell follicles, and decreased viral loads in CAR/CXCR5-T cell treated ART-suppressed Simian immunodeficiency virus- infected NHPs compared to controls. Our human CAR/CXCR5-T cells also show CXCR5-driven migratory and anti-HIV killing characteristics in vitro, showing promise as a treatment for people living with HIV. FDA-approved CAR-T cell therapies are successful in treating various cancers; however, the processes to produce the CAR- T cells are complex, involving leukapheresis and ex-vivo manipulation of peripheral blood mononuclear cells prior to reinfusion back to the patient. Thus, recent efforts are focused on developing universal, off-the-shelf in vivo-produced CAR-T cell therapies, including the use of adeno-associated virus (AAV) gene delivery systems. Since the process to produce an off-the-shelf AAV gene therapy is a fraction of the complexity of ex-vivo production of CAR-T cells individualized for each patient, the expectation is that AAV gene therapy to produce CAR/CXCR5-T cells will eventually prove to be less costly than current life-long therapy for HIV, which is estimated at over $500,000. To develop an off-the-shelf in vivo CAR/CXCR5-T cell product, this proposal seeks to perform the necessary first steps of producing receptor-targeted, AAV-directed CAR-T cells (second generation [2G] -CAR/CXCR5-T cells) in vitro and assessing their targeted efficacy against HIV. Using our intellectual property-protected technology to assemble AAV composites for receptor-targeted gene delivery, we propose in vitro proof-of-concept studies to produce receptor-targeted, AAV-directed 2G-CAR/CXCR5-T cells using AAV composites containing anti-CD5 monoclonal antibody (CD5mab) and carrying a 2G-CAR/CXCR5 DNA payload. As T cells specifically express CD5 on their cell surface, AAV-CD5mab composites carrying 2G- CAR/CXCR5 DNA payload (AAV-CD5mab-2G-CAR/CXCR5) are expected to specifically bind CD5 on T cells and transduce them, thereby producing functional 2G-CAR/CXCR5-T cells that home to B cell follicles in vivo. Successful completion of the proposed studies will lay the groundwork not only for Phase II IND-enabling studies for in vivo HIV 2G-CAR/CXCR5-T cells, but also for other therapeutic ... ## Key facts - **NIH application ID:** 10920053 - **Project number:** 1R41AI184054-01 - **Recipient organization:** MARPAM PHARMA, LLC - **Principal Investigator:** Maria Constance Athanasiou - **Activity code:** R41 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $302,248 - **Award type:** 1 - **Project period:** 2024-03-15 → 2025-02-28 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10920053 ## Citation > US National Institutes of Health, RePORTER application 10920053, Proof of concept studies for in vivo produced CAR-T cells that target B cell follicles as a treatment for HIV (1R41AI184054-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10920053. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*