# Bifunctional Chimeric Antigen Receptors for clearing HIV

> **NIH NIH R33** · BAYLOR COLLEGE OF MEDICINE · 2020 · $490,909

## Abstract

   
DESCRIPTION (provided by applicant): While combination antiretroviral therapy (cART) is effective at suppressing HIV, it fails to eradicate latent provirus or restore virus-specific T-cel responses that can eliminate virus-expressing cells after induction with a latency reversing agent or treatment interruption. One potential way is to create designer HIV-specific T- cells for use by adoptive T-cell therapy, which has shown promise for treating other viral infections and cancer in clinical trials. In this application, we proposed to develop a chimeric antigen receptor (CAR) specific for the HIV-1 envelope protein (Anti-HIV-1 Env-CAR), which when expressed on modified T-cells, is capable of protecting the modified T-cells from infection and triggering T-cel responses required for the clearance of infected cells. Two findings serve as the basis for the anti-HIV-1 Env-CAR. First, our past studies have demonstrated that some single chain variable fragments (scFvs) of anti-HIV Env antibodies are potent inhibitors of HIV-1 when expressed on the surface of target cells. Second, the co-investigator and others have demonstrated the potential for adoptive T-cell therapy for treating viral infections and cancer, and the promise for
CARs to improve persistence and anti-tumor activity of engineered T-cells. They have also demonstrate the capacity to expand broadly-specific polyclonal T-cells that can clear HIV-infected cells. We hypothesize that combining a neutralizing anti-HIV Env scFv with a second generation CD28ζ-CAR having activation and costimulatory properties will result in a bifunctional CAR (anti-HIV Env-CD28ζ) molecule that promotes proliferation and anti-HIV T-cell responses in modified T-cells while protecting them from HIV infection and cell death. This CAR could be used to recognized and eliminate latently infected cells after induction of viral gene expression with a latency reversing agent. The hypothesis will be addressed in three specific aims. Aim1 will examine whether ex vivo expanded T-cells modified with the anti-HIV Env-CD28ζ CAR will direct Env-specific T-cell responses and killing of infected target cells. Aim2 wil examine whether the anti-HIV Env-CD28ζ protects modified T-cells from infection by diverse HIV-1 variants. Aim3 will determine whether anti-Env- CD28ζ CAR modified T-cells enhance HIV-1 infected cell clearance and decrease viral loads in a humanized mouse model. Successful completion of this project will advance the potential for using CAR modified T-cells for targeting and eliminating latent HIV reservoirs after reactivation, a primary goal of the TaPHIR R21/R33 program.

## Key facts

- **NIH application ID:** 9977951
- **Project number:** 5R33AI116167-05
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** JASON T. KIMATA
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $490,909
- **Award type:** 5
- **Project period:** 2016-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977951

## Citation

> US National Institutes of Health, RePORTER application 9977951, Bifunctional Chimeric Antigen Receptors for clearing HIV (5R33AI116167-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9977951. Licensed CC0.

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