# Dual CMV and HIV CARs for Cure of HIV

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $195,000

## Abstract

PROJECT SUMMARY/ABSTRACT
CD8+ cytotoxic T lymphocytes (CTLs) play a key role protective role in the immunopathogenesis of HIV-1
infection, but eventually fail in most persons due to lagging behind the virus. Numerous data indicate that HIV-
1-specific CTLs mediate the suppression of HIV-1 that mediates the “asymptomatic phase” of chronic infection.
The CTL response arises by clonal expansion from the naïve cell population, and once the antigen is cleared
to low or absent levels, most of these cells die, leaving resting central memory cells with low effector function,
but which are primed for more rapid expansion upon re-challenge to effector cells. This process results in the
lag of CTLs behind HIV-1, and viral sequence evolution outpaces CTLs to allow mutational escape during
established infection that is likely a major mechanism of viral persistence leading to CTL exhaustion and
eventual failure. Although treatment with antiretroviral therapy (ART) stops most ongoing viral replication and
could potentially allow immune regeneration that could control infection after treatment interruption, CTL
responses to decay to resting memory levels, and treatment interruption usually leads to a rapid rise in viremia
similar to acute infection.
We hypothesize that continuously driving persistence of effector CTLs against HIV-1 could interrupt this
pathogenic cycle. Rather than allowing CTLs to lag behind HIV-1, we propose a strategy to maintain levels of
HIV-1-specific effector CTLs independently of HIV-1 replication. This could prevent (in the case of an
uninfected person) or break (in the case of an infected person on ART) the pathogenic cycle leading to CTL
dysfunction. To achieve this goal, we will take advantage of the in vivo chronic antigenic stimulus of human
cytomegalovirus (CMV) to drive CTLs that recognize both CMV and HIV-1. Specifically, we aim:
 1. To engineer lentiviral vectors that generate CAR T cells targeting CMV and HIV-1 simultaneously;
 2. To confirm the function of these vectors in vitro as a prerequisite for future animal studies.

## Key facts

- **NIH application ID:** 10001141
- **Project number:** 1R21AI136606-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** OTTO O YANG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $195,000
- **Award type:** 1
- **Project period:** 2020-03-05 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001141

## Citation

> US National Institutes of Health, RePORTER application 10001141, Dual CMV and HIV CARs for Cure of HIV (1R21AI136606-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10001141. Licensed CC0.

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