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Review
. 2023 Mar 19;15(3):789.
doi: 10.3390/v15030789.

Opportunities for CAR-T Cell Immunotherapy in HIV Cure

Gerard Campos-Gonzalez  1 , Javier Martinez-Picado  1   2   3   4   5 , Talia Velasco-Hernandez  6   7 , Maria Salgado  1   4   5
Affiliations
Review

Opportunities for CAR-T Cell Immunotherapy in HIV Cure

Gerard Campos-Gonzalez et al. Viruses. .

Abstract

Chimeric antigen receptor (CAR) technology is having a huge impact in the blood malignancy field and is becoming a well-established therapy for many types of leukaemia. In recent decades, efforts have been made to demonstrate that CAR-T cells have potential as a therapy to achieve a sterilizing cure for human immunodeficiency virus (HIV) infection. However, translation of this technology to the HIV scenario has not been easy, as many challenges have appeared along the way that hinder the consolidation of CAR-T cells as a putative therapy. Here, we review the origin and development of CAR-T cells, describe the advantages of CAR-T cell therapy in comparison with other therapies, and describe the major obstacles currently faced regarding application of this technology in the HIV field, specifically, viral escape, CAR-T cell infectivity, and accessibility to hidden reservoirs. Nonetheless, promising results in successfully tackling some of these issues that have been obtained in clinical trials suggest a bright future for CAR-T cells as a consolidated therapy.

Keywords: CAR-T cells; HIV; HIV reservoir; chimeric antigen receptor; immunotherapy; latency reversal agents.

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Conflict of interest statement

J.M-P. has received institutional grants and educational/consultancy fees from AbiVax, AstraZeneca, Gilead Sciences, Grifols, Janssen, Merck Sharp & Dohme, and ViiV Healthcare, all outside the submitted work. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the main limitations of CAR-T cells as a therapy for HIV and new approaches to overcome the limitations. (A) CD4-CAR-T cells can be infected by HIV-1 through interaction with CD4 and CCR5 receptors present in the CAR. Alternative approaches proposed: (i) use of bNAbs to build the CAR; (ii) deletion of the CCR5 gene through gene editing techniques to prevent infection; or (iii) both approaches combined. (B) The high mutation rate of HIV-1 can generate HIV-1 strains resistant to the CAR-T cell cytotoxic effect. Some of the new CAR-T cell designs: (i) duoCAR-T cells, which are able to target more than one gp160 epitope, and (ii) convertibleCAR-T built with a common binding site for a variety of gp160-specific bNAbs that can mitigate viral escape. (C) Latently infected cells from reservoirs are not accessible to CAR-T cells, but shock-and-kill approaches such as using LRAs can transcriptionally reactivate these cells making them accessible targets for CAR-T cells.
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