# Development of a treatment for the durable remission of HIV using autologous human CAR T cells that target B cell follicles

> **NIH NIH R41** · MARPAM PHARMA, LLC · 2021 · $52,000

## Abstract

Abstract
Building on our successful primate model studies, we aim to develop a one-time treatment for durable remission
of human immunodeficiency virus (HIV) in the absence of antiretroviral medications. This treatment is an
autologous HIV-specific chimeric antigen receptor (CAR, specifically CD4-MBL-CAR) T cell therapy that targets
B cell follicles1,2. B cell follicles are an immune protected site that permit viral replication due to low levels of
virus-specific CD8 T cells3–6. Our preclinical CAR T cell pilot studies in a simian immunodeficiency virus (SIV)-
infected rhesus macaque model of HIV indicated that this immunotherapy is safe and effective. Here, we
propose to develop and evaluate a comparable human T cell immunotherapy. Virus-specific CD8 T cells exert
potent antiviral activity against HIV-1 and SIV both in vitro and in vivo. Nevertheless, despite abundant CD8 T
cell responses in HIV-1-infected humans and SIV-infected macaques, these cells are unable to fully suppress
virus replication. This inadequate suppression is likely due to the fact that the majority of HIV-1 and SIV
replication occurs in CD4+ T cells7–11 concentrated within B cell follicles in secondary lymphoid tissues, where
relatively few virus-specific CD8 T cells reside3–6. In fact, we showed that the effector to target ratio of in vivo
effector virus-specific CD8 T cell to target SIV RNA+ cells is >40-fold lower inside compared to outside of B cell
follicles in lymphoid tissues during SIV infection in rhesus macaque5. Furthermore, we revealed that the majority
of virus-specific CD8 T cells fail to express the follicular homing molecule CXCR55, likely explaining low levels
of virus-specific CD8 T cells localizing to and surveilling B cell follicles. These data suggest that the inability of
HIV- and SIV-specific CD8 T cells to fully suppress virus replication may be due to a deficiency of virus-specific
CD8 T cells in B cell follicles. Based on these findings and the success of our preclinical primate studies, we
propose to develop an HIV-specific CD4-MBL-CAR T cell therapy that employs the follicular homing
molecule CXCR5 to direct the migration of HIV-specific T cells to B cell follicles. We specifically propose
the following aims, 1) Develop human CD4-MBL-CAR/CXCR5 T cells, 2) Determine the phenotype of human
CD4-MBL-CAR/CXCR5 T cells, 3) Determine the function of human CD4-MBL-CAR/CXCR5 T cells. Our
proposed studies to develop human CD4-MBL-CAR/CXCR5 T cells that localize to and function in lymphoid
B cell follicles may lead to durable remission of HIV infection in the absence of antiretroviral drugs.

## Key facts

- **NIH application ID:** 10348815
- **Project number:** 3R41AI155031-01S1
- **Recipient organization:** MARPAM PHARMA, LLC
- **Principal Investigator:** Maria Constance Athanasiou
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $52,000
- **Award type:** 3
- **Project period:** 2020-06-18 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348815

## Citation

> US National Institutes of Health, RePORTER application 10348815, Development of a treatment for the durable remission of HIV using autologous human CAR T cells that target B cell follicles (3R41AI155031-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10348815. Licensed CC0.

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