NIH grant: Engineering NK Cells for Effective HIV Reservoir Targeting (ENHANCE) (1R01AI197995-01A1)

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NIH grant 1R01AI197995-01A1: Engineering NK Cells for Effective HIV Reservoir Targeting (ENHANCE)
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Jocelyn T Kim. Award: $793623.
Start: 2026-08-27T00:00:00.
PROJECT SUMMARY/ABSTRACT
Despite the success of antiretroviral therapy (ART) in suppressing HIV replication, it fails to eradicate the virus
due to the persistence of latent reservoirs. Upon cessation of ART, rapid viral rebound occurs, underscoring the
need for strategies that eliminate these reservoirs. This project aims to develop engineered natural killer (NK)
cells with enhanced anti-HIV targeting, cytotoxicity, persistence, and homing capabilities. By incorporating
chimeric antigen receptors (CARs) targeting HIV envelope proteins and activating NK cell receptors, and
integrating intracellular cytokine signaling domains, we seek to optimize NK cell function without the need for
exogenous cytokines. The engineered CAR-NK cells will be evaluated across a comprehensive suite of models,
including 2D in vitro cultures, ex vivo assays using latently infected cells from people living with HIV, 3D human
lymphoid organoids, and humanized mice infected with barcoded HIV. Combining these optimized NK cells with
potent latency reversing agents aims to achieve an “induce and reduce” strategy for reservoir clearance.
Successful completion of this project could lead to a scalable, off-the-shelf CAR-NK cell therapy capable of
durable HIV reservoir elimination, advancing efforts toward a functional cure.

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