# Induction of autophagy to enhance CAR-T cells in HIV cure approaches

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $795,998

## Abstract

ABSTRACT
 Chimeric Antigen Receptor (CAR) T-cells have emerged as a promising immunotherapy in controlling
HIV-1 infection. However, CAR-T cells are also subject to immune dysfunction/exhaustion mediated by
persistent inflammation during chronic HIV infection. Strategies to prevent exhaustion/restore functions of anti-
HIV CAR-T cell are critical for ultimately achieving HIV functional cure. Our preliminary studies have showed
that autophagy induction can improve mitochondria function and promote CAR-T cell cytotoxic T lymphocyte
activity in vitro. Importantly, we found that induction of autophagy can prevent excessive IFN-I signaling and in
vivo treatment with autophagy inducer rapamycin in chronically HIV infected humanized mice can decrease
inflammation, restore exhausted anti-viral T cell function, and reduce viral loads. In addition, we found that
autophagy inducers such as rapamycin allow efficient HIV-1 latency reversal by PKC activator bryostatin-1
while reducing T cell activation associated immune toxicity. Therefore, we hypothesize that autophagy
induction can enhance ‘kick and kill’ HIV cure approaches by improving the survival, persistence and function
of anti-HIV CAR-T cells and facilitating effective and safe latency reversal by PKC modulators. We will utilize
our well-established humanized mouse model engineered with anti-HIV CD4CAR T cells to investigate the
therapeutic potentials of autophagy induction for HIV ‘kick and kill’ cure approaches. Our study will also provide
mechanistic insights into the development of immune exhaustion and autophagy’s regulation of CAR-T cell
function and will thus have a wide impact beyond HIV cure research.

## Key facts

- **NIH application ID:** 10550477
- **Project number:** 1R01AI172727-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Matthew David Marsden
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $795,998
- **Award type:** 1
- **Project period:** 2022-06-25 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10550477

## Citation

> US National Institutes of Health, RePORTER application 10550477, Induction of autophagy to enhance CAR-T cells in HIV cure approaches (1R01AI172727-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10550477. Licensed CC0.

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