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Therapeutic Targeting of HIV Reservoirs: How to Give T Cells a New Direction
HIV cannot be cured by current antiretroviral therapy (ART) because it persists in a transcriptionally silent form in long-lived CD4+ cells. Leading efforts to develop a functional cure have prioritized latency reversal to expose infected cells to immune surveillance, coupled with enhancement of the...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288286/ https://www.ncbi.nlm.nih.gov/pubmed/30564246 http://dx.doi.org/10.3389/fimmu.2018.02861 |
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author | Yang, Hongbing Wallace, Zoë Dorrell, Lucy |
author_facet | Yang, Hongbing Wallace, Zoë Dorrell, Lucy |
author_sort | Yang, Hongbing |
collection | PubMed |
description | HIV cannot be cured by current antiretroviral therapy (ART) because it persists in a transcriptionally silent form in long-lived CD4+ cells. Leading efforts to develop a functional cure have prioritized latency reversal to expose infected cells to immune surveillance, coupled with enhancement of the natural cytolytic function of immune effectors, or “kick and kill.” The most clinically advanced approach to improving the kill is therapeutic immunization, which aims to augment or re-focus HIV-specific cytolytic T cell responses. However, no vaccine strategy has enabled sustained virological control after ART withdrawal. Novel approaches are needed to overcome the limitations of natural adaptive immune responses, which relate to their specificity, potency, durability, and access to tissue reservoirs. Adoptive T cell therapy to treat HIV infection was first attempted over two decades ago, without success. Since then, progress in the field of cancer immunotherapy, together with recognition of the similarities in tumor microenvironments and HIV reservoirs has reignited interest in the application of T cell therapies to HIV eradication. Advances in engineering of chimeric antigen receptor (CAR)-transduced T cells have led to improved potency, persistence and latterly, resistance to HIV infection. Immune retargeting platforms have incorporated non-neutralizing and broadly neutralizing antibodies to generate Bispecific T cell Engagers (BiTEs) and Dual-Affinity Re-Targeting proteins (DARTs). T cell receptor engineering has enabled the development of the first bispecific Immune-mobilizing monoclonal T Cell receptors Against Viruses (ImmTAV) molecules. Here, we review the potential for these agents to provide a better “kill” and the challenges ahead for clinical development. |
format | Online Article Text |
id | pubmed-6288286 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62882862018-12-18 Therapeutic Targeting of HIV Reservoirs: How to Give T Cells a New Direction Yang, Hongbing Wallace, Zoë Dorrell, Lucy Front Immunol Immunology HIV cannot be cured by current antiretroviral therapy (ART) because it persists in a transcriptionally silent form in long-lived CD4+ cells. Leading efforts to develop a functional cure have prioritized latency reversal to expose infected cells to immune surveillance, coupled with enhancement of the natural cytolytic function of immune effectors, or “kick and kill.” The most clinically advanced approach to improving the kill is therapeutic immunization, which aims to augment or re-focus HIV-specific cytolytic T cell responses. However, no vaccine strategy has enabled sustained virological control after ART withdrawal. Novel approaches are needed to overcome the limitations of natural adaptive immune responses, which relate to their specificity, potency, durability, and access to tissue reservoirs. Adoptive T cell therapy to treat HIV infection was first attempted over two decades ago, without success. Since then, progress in the field of cancer immunotherapy, together with recognition of the similarities in tumor microenvironments and HIV reservoirs has reignited interest in the application of T cell therapies to HIV eradication. Advances in engineering of chimeric antigen receptor (CAR)-transduced T cells have led to improved potency, persistence and latterly, resistance to HIV infection. Immune retargeting platforms have incorporated non-neutralizing and broadly neutralizing antibodies to generate Bispecific T cell Engagers (BiTEs) and Dual-Affinity Re-Targeting proteins (DARTs). T cell receptor engineering has enabled the development of the first bispecific Immune-mobilizing monoclonal T Cell receptors Against Viruses (ImmTAV) molecules. Here, we review the potential for these agents to provide a better “kill” and the challenges ahead for clinical development. Frontiers Media S.A. 2018-12-04 /pmc/articles/PMC6288286/ /pubmed/30564246 http://dx.doi.org/10.3389/fimmu.2018.02861 Text en Copyright © 2018 Yang, Wallace and Dorrell. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Yang, Hongbing Wallace, Zoë Dorrell, Lucy Therapeutic Targeting of HIV Reservoirs: How to Give T Cells a New Direction |
title | Therapeutic Targeting of HIV Reservoirs: How to Give T Cells a New Direction |
title_full | Therapeutic Targeting of HIV Reservoirs: How to Give T Cells a New Direction |
title_fullStr | Therapeutic Targeting of HIV Reservoirs: How to Give T Cells a New Direction |
title_full_unstemmed | Therapeutic Targeting of HIV Reservoirs: How to Give T Cells a New Direction |
title_short | Therapeutic Targeting of HIV Reservoirs: How to Give T Cells a New Direction |
title_sort | therapeutic targeting of hiv reservoirs: how to give t cells a new direction |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288286/ https://www.ncbi.nlm.nih.gov/pubmed/30564246 http://dx.doi.org/10.3389/fimmu.2018.02861 |
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