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

> **NIH NIH R42** · MARPAM PHARMA, LLC · 2022 · $1,009,537

## Abstract

ABSTRACT
MarPam Pharma is developing a one-time treatment for durable remission of human immunodeficiency virus
(HIV) for patients treated with antiretroviral therapy (ART). This treatment is an autologous HIV-specific chimeric
antigen receptor (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 located in lymphoid follicles1,2. B
cell follicles are an immune protected site where the majority of viral replication can occur relatively unabated in
CD4+ T cells3-7, likely due to a markedly lower presence of virus-specific CD8 T cells inside compared to outside
of B cell follicles in lymphoid tissue8-11. In fact, few virus-specific CD8 T cells express the follicular homing
molecule CXCR510, possibly explaining the 40-fold lower in vivo effector CTL to target vRNA+ cell levels inside
compared to outside of B cell follicles10. These findings suggest that the inability of HIV-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.
Importantly, pilot studies of this CAR-T cell treatment showed safety in animals and also successful homing of
CAR-T cells to B cell follicles, evidence of direct contact of the CAR-T cells with viral RNA+ infected cells, and
decreased viral loads in ART-suppressed rhesus macaques infected with simian immunodeficiency virus (SIV),
a model of HIV. Here, we propose to conduct an IND-enabling preclinical study to assess the safety and efficacy
of autologous CAR-T cells transduced with the human CAR construct in a study statistically powered to
demonstrate efficacy in a rhesus macaque simian-human immunodeficiency virus (SHIV) model of HIV. In our
recent STTR Phase 1 studies, we successfully produced human CAR-T cells using a small-scale research
method. Here, we propose to develop a scalable method for GMP production of gammaretrovirus and
CAR/CXR5-T cells. These proposed studies will move our product from the current preclinical stage of
development into clinical development.

## Key facts

- **NIH application ID:** 10465273
- **Project number:** 5R42AI155031-03
- **Recipient organization:** MARPAM PHARMA, LLC
- **Principal Investigator:** Maria Constance Athanasiou
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,009,537
- **Award type:** 5
- **Project period:** 2020-06-18 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465273

## Citation

> US National Institutes of Health, RePORTER application 10465273, Development of a treatment for the durable remission of HIV using autologous human CAR T cells that target B cell follicles (5R42AI155031-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10465273. Licensed CC0.

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