# CAR T CELLS ENGINEERED TO KILL HIV-INFECTED CELLS WHILE SECRETING BROADLY NEUTRALIZING ANTIBODIES

> **NIH NIH R01** · SCINTILLON INSTITUTE FOR PHOTOBIOLOGY · 2020 · $422,400

## Abstract

PROJECT SUMMARY
 A cure for HIV requires the elimination of the latently-infected pool of host cells harboring HIV provirus,
but this has proven quite difficult and remains a major obstacle in the field. Currently, several chemical latency
reversing agents have been described, however, their in vivo efficacy has not been demonstrated. Thus, the
need for new approaches to address this issue is urgently needed. One attractive method to combat HIV
latency, would be a self-sustaining curative to endlessly surveil the host rapidly killing newly activated reservoir
cells before the release of a significant amount of virus. Previously, T cells transduced to express CD4 on their
surface linked to activation signaling machinery, chimeric antigen receptor (CAR) T cells, were employed to
target and kill infected host cells. But there were substantial drawbacks with this approach, including a novel
entry route for infection of CD8 T cells, shielding of the CD4-binding site, and lack of efficacy. Utilizing secreted
high-affinity anti-HIV bnAbs, which are remarkably effective across a wide swath of HIV strains, in conjunction
with superior CAR designs, we here propose to exploit both advancements to generate doubly
immunotherapeutic improved CAR T cells. These pioneering studies will provide new insights into how to
access and control the reservoir of latently HIV-infected cells and, in combination with ART, address the
exigent goal of functional control of HIV. Upon completion of this project, we expect to have several validated
CAR T cell constructs ready for future testing in SHIV non-human primate models and/or perhaps humans.
Since these studies utilize autologous T cells, we expect to see very few adverse events. Moreover, if
successful, life-long use of anti-retrovirals, which have been associated with toxicity, is likely to be reduced or
perhaps eliminated by this approach.

## Key facts

- **NIH application ID:** 10242235
- **Project number:** 7R01AI150381-02
- **Recipient organization:** SCINTILLON INSTITUTE FOR PHOTOBIOLOGY
- **Principal Investigator:** Brian Lawson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $422,400
- **Award type:** 7
- **Project period:** 2020-03-25 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242235

## Citation

> US National Institutes of Health, RePORTER application 10242235, CAR T CELLS ENGINEERED TO KILL HIV-INFECTED CELLS WHILE SECRETING BROADLY NEUTRALIZING ANTIBODIES (7R01AI150381-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242235. Licensed CC0.

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