# Biomaterials-Enhanced NK Cells for Improved Elimination of the HIV Reservoir

> **NIH NIH R33** · GEORGE WASHINGTON UNIVERSITY · 2021 · $485,681

## Abstract

PROJECT SUMMARY
Highly active antiretroviral therapy has reduced morbidity and mortality from HIV/AIDS but does not lead to a
cure. The persistence of the virus within latent reservoirs even in well-treated individuals results in a lifelong
commitment to these drug regimens. As a consequence, patients remain burdened by co-morbidities and
exposed to the negative social issues that come with being HIV-positive. Therefore, there is an urgent need for
the development of therapeutic strategies capable of eradicating virus from individuals, which would greatly
improve the lives of people living with HIV/AIDS. In response to this need, we propose to combine the actions
of latency reversing agents (LRAs), broadly neutralizing antibodies (bnAbs), and activated natural killer (NK)
cells within a single therapeutic platform. More specifically, we propose to use bioengineering strategies to
design an ensemble biohybrid therapeutic wherein LRAs and bnAbs are packaged within poly(lactic-co-glycolic
acid) (PLGA) nanoparticle depots (nanodepots) and then attached on to the surface of NK cells. We anticipate
that the co-localization of LRAs with NK cell activation and local bnAb presence will trigger a more effective
and coordinated eradication of persistent HIV reservoirs. In the R21 phase of this project, we propose to
engineer NK-nanodepots encapsulating LRAs and bnAbs as off-the-shelf biohybrids that retain the phenotype
and function of the constituent NK cells and encapsulated LRAs and bnAbs. The realization of a functional
ensemble biohybrid therapeutic that successfully coordinates the actions of LRAs, bnAbs, and NK cells will
enable us to proceed to the R33 phase of the project where we will test the efficacy of the ensemble biohybrid
therapeutic in eradicating the HIV reservoir in vitro and in a humanized mouse model. Successful completion of
this phase of the project will result in a novel therapeutic platform for eradicating persistent HIV reservoirs and
will open the way for the translation of our platform to the design and conduct of future clinical trials.

## Key facts

- **NIH application ID:** 10247828
- **Project number:** 5R33AI136102-04
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Conrad Russell Young Cruz
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $485,681
- **Award type:** 5
- **Project period:** 2018-01-03 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247828

## Citation

> US National Institutes of Health, RePORTER application 10247828, Biomaterials-Enhanced NK Cells for Improved Elimination of the HIV Reservoir (5R33AI136102-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10247828. Licensed CC0.

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