# Targeting HIV-specific CAR T cells to the gut for the durable remission of HIV

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2024 · $674,347

## Abstract

Abstract
Virus-specific CD8 T cells exert potent antiviral activity against HIV-1 and SIV. Despite abundant
CD8 T cell responses, these are unable to fully suppress virus replication. This is likely due to
the majority of viral replication occurring in CD4+ T cells concentrated in specific areas in the
body, such as B-cell follicles in secondary lymphoid tissues and in intestinal tissues. Viral
reservoir studies indicate that the majority of SIV and HIV replication may occur in the intestinal
mucosa: After ART interruption, the location, abundance, and phenotype of recrudescing virally
infected cells are not well understood. However, emerging data suggest that both CD4 T cells,
as well as myeloid cells, in lymph node (LN) and the intestine are important contributors. Thus,
there is a need to develop methods to reduce viral load in mucosal tissues, as well as in LN,
and to more fully understand the source of viral reservoirs in non-lymphoid tissues. CAR T cells
can be potent mediators of immune control and these are being explored as an HIV therapy. We
have developed and begun testing an HIV/SIV targeting CAR. In this study, we have developed
and propose to test autologous T cells engineered to express the HIV-targeting CAR and CCR9,
a molecule that will target cells to the intestinal mucosa. We will test our hypothesis that
targeting HIV-specific T cells to the intestinal mucosa, as well as B cell follicles, will lead to
durable remission of HIV. We propose two aims to test the hypothesis. Aim 1: to determine the
in vivo localization, persistence and antiviral efficacy and impact on intestinal mucosa, lymphoid
tissue, and other tissue viral reservoirs in SIV infected ART suppressed rhesus macaques
infused with autologous CAR/CCR9 T cells. Aim 2: to determine whether combination therapy
using both intestine- and lymphoid follicle-homing CAR T cells is superior in promoting
sustained remission of SIV after antiretroviral drug treatment interruption. If successful, this work
may lead to an immunotherapy that leads to long-term suppression of HIV.

## Key facts

- **NIH application ID:** 10818327
- **Project number:** 5R01DK133907-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** PAMELA J SKINNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $674,347
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10818327

## Citation

> US National Institutes of Health, RePORTER application 10818327, Targeting HIV-specific CAR T cells to the gut for the durable remission of HIV (5R01DK133907-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10818327. Licensed CC0.

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