T-cell therapies for HIV

Abstract

Antiretroviral therapy has improved the quality of life for HIV(+) individuals but efficacy requires strict adherence and treatment is not curative. Recently, the use of T cells as therapeutic agents has been in the spotlight in the settings of post-transplant opportunistic infections and cancer. Whether T-cell therapy can be harnessed for treating HIV remains to be determined but there are a few studies that seek to answer that question. Infusion of ex vivo-expanded HIV-specific T cells showed limited efficacy but no adverse events. Genetically modified T cells expressing CD4 chimeric antigen receptors have recently been shown to have persistence that outperforms chimeric antigen receptors used for cancers. Although the results have not yet been published for many clinical studies using T cells for HIV, preclinical studies and the clinical data that are available highlight the potential for T-cell therapy to decrease or eliminate HIV patients' dependency on antiretroviral therapy.

Figure 1. Strategies to improve anti-HIV T cells

T cells can be modified to more effectively target HIV infected cells by increasing the specificity to HIV antigens. This can be achieved by genetically modifying T cells with a chimeric antigen receptor (CAR) or an artificial T cell receptor that may have extraordinarily high affinity to HIV epitopes. T cells can also be stimulated using peptides or mRNA for HIV antigens. HIV-specific T cells can be enriched for memory phenotypes prior to infusion which have more potential for persistence versus effector T cells. HIV entry can also be inhibited to protect the CD4 pool, allowing immune reconstitution as well as supporting CD8 T cell activity.