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Immunotherapy with Cell-Based Biological Drugs to Cure HIV-1 Infection

Since its discovery 35 years ago, there have been no therapeutic interventions shown to enable full HIV-1 remission. Combined antiretroviral therapy (cART) has achieved the sustained control of HIV-1 replication, however, the life-long treatment does not eradicate long-lived latently infected reserv...

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Autores principales: Siracusano, Gabriel, Lopalco, Lucia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750418/
https://www.ncbi.nlm.nih.gov/pubmed/35011639
http://dx.doi.org/10.3390/cells11010077
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author Siracusano, Gabriel
Lopalco, Lucia
author_facet Siracusano, Gabriel
Lopalco, Lucia
author_sort Siracusano, Gabriel
collection PubMed
description Since its discovery 35 years ago, there have been no therapeutic interventions shown to enable full HIV-1 remission. Combined antiretroviral therapy (cART) has achieved the sustained control of HIV-1 replication, however, the life-long treatment does not eradicate long-lived latently infected reservoirs and can result in multiple side effects including the development of multidrug-resistant escape mutants. Antibody-based treatments have emerged as alternative approaches for a HIV-1 cure. Here, we will review clinical advances in coreceptor-targeting antibodies, with respect to anti-CCR5 antibodies in particular, which are currently being generated to target the early stages of infection. Among the Env-specific antibodies widely accepted as relevant in cure strategies, the potential role of those targeting CD4-induced (CD4i) epitopes of the CD4-binding site (CD4bs) in eliminating HIV-1 infected cells has gained increasing interest and will be presented. Together, with approaches targeting the HIV-1 replication cycle, we will discuss the strategies aimed at boosting and modulating specific HIV-1 immune responses, highlighting the harnessing of TLR agonists for their dual role as latency reverting agents (LRAs) and immune-modulatory compounds. The synergistic combinations of different approaches have shown promising results to ultimately enable a HIV-1 cure.
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spelling pubmed-87504182022-01-12 Immunotherapy with Cell-Based Biological Drugs to Cure HIV-1 Infection Siracusano, Gabriel Lopalco, Lucia Cells Review Since its discovery 35 years ago, there have been no therapeutic interventions shown to enable full HIV-1 remission. Combined antiretroviral therapy (cART) has achieved the sustained control of HIV-1 replication, however, the life-long treatment does not eradicate long-lived latently infected reservoirs and can result in multiple side effects including the development of multidrug-resistant escape mutants. Antibody-based treatments have emerged as alternative approaches for a HIV-1 cure. Here, we will review clinical advances in coreceptor-targeting antibodies, with respect to anti-CCR5 antibodies in particular, which are currently being generated to target the early stages of infection. Among the Env-specific antibodies widely accepted as relevant in cure strategies, the potential role of those targeting CD4-induced (CD4i) epitopes of the CD4-binding site (CD4bs) in eliminating HIV-1 infected cells has gained increasing interest and will be presented. Together, with approaches targeting the HIV-1 replication cycle, we will discuss the strategies aimed at boosting and modulating specific HIV-1 immune responses, highlighting the harnessing of TLR agonists for their dual role as latency reverting agents (LRAs) and immune-modulatory compounds. The synergistic combinations of different approaches have shown promising results to ultimately enable a HIV-1 cure. MDPI 2021-12-28 /pmc/articles/PMC8750418/ /pubmed/35011639 http://dx.doi.org/10.3390/cells11010077 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Siracusano, Gabriel
Lopalco, Lucia
Immunotherapy with Cell-Based Biological Drugs to Cure HIV-1 Infection
title Immunotherapy with Cell-Based Biological Drugs to Cure HIV-1 Infection
title_full Immunotherapy with Cell-Based Biological Drugs to Cure HIV-1 Infection
title_fullStr Immunotherapy with Cell-Based Biological Drugs to Cure HIV-1 Infection
title_full_unstemmed Immunotherapy with Cell-Based Biological Drugs to Cure HIV-1 Infection
title_short Immunotherapy with Cell-Based Biological Drugs to Cure HIV-1 Infection
title_sort immunotherapy with cell-based biological drugs to cure hiv-1 infection
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750418/
https://www.ncbi.nlm.nih.gov/pubmed/35011639
http://dx.doi.org/10.3390/cells11010077
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