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Supraphysiologic control over HIV-1 replication mediated by CD8 T cells expressing a re-engineered CD4-based chimeric
Rachel S Leibman1,2, Max W Richardson1,2, Christoph T Ellebrecht3
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Plos Pathogens
|October 13, 2017
Summary
Researchers engineered chimeric antigen receptor (CAR) T cells to enhance HIV control. Optimized CAR T cells showed superior potency in vitro and in vivo, offering a promising strategy for HIV cure.
Area of Science:
- Immunology
- Virology
- Biotechnology
Background:
- HIV evades natural T cell responses, necessitating more potent therapeutic strategies.
- Existing T cell-based approaches require enhancement for effective HIV control.
Purpose of the Study:
- To re-engineer chimeric antigen receptor (CAR) T cells for improved potency against HIV.
- To evaluate the efficacy of optimized CAR T cells in controlling HIV replication in vitro and in vivo.
Main Methods:
- Optimization of CAR vector backbone, promoter, HIV targeting moiety, and signaling domains.
- In vitro assessment of CAR T cell potency against HIV replication.
- In vivo studies using humanized mouse models of HIV infection and treatment.
Main Results:
- Re-engineered CAR T cells demonstrated at least 50-fold greater potency in vitro compared to original CARs and TCR-based approaches.
- Optimized CAR T cells showed superior expansion, CD4 T cell protection, and viral load reduction in a humanized mouse model.
- CD4 CAR T cells with a 4-1BB costimulatory domain exhibited better control of HIV spread post-ART removal.
Conclusions:
- Improved CAR design can generate potent HIV-specific T cells.
- CAR T cells represent a promising component for future HIV cure strategies.
