Evolving Strategies to Eliminate the CD4 T Cells HIV Viral Reservoir via CAR T Cell Immunotherapy
Although the advent of ART has significantly reduced the morbidity and mortality associated with HIV infection, the stable pool of HIV in latently infected cells requires lifelong treatment adherence, with the cessation of ART resulting in rapid reactivation of the virus and productive HIV infection...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.873701/full |
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| author | Jarrod York Jarrod York Kavitha Gowrishankar Kavitha Gowrishankar Kavitha Gowrishankar Kenneth Micklethwaite Kenneth Micklethwaite Kenneth Micklethwaite Kenneth Micklethwaite Sarah Palmer Sarah Palmer Anthony L. Cunningham Anthony L. Cunningham Najla Nasr Najla Nasr |
| author_facet | Jarrod York Jarrod York Kavitha Gowrishankar Kavitha Gowrishankar Kavitha Gowrishankar Kenneth Micklethwaite Kenneth Micklethwaite Kenneth Micklethwaite Kenneth Micklethwaite Sarah Palmer Sarah Palmer Anthony L. Cunningham Anthony L. Cunningham Najla Nasr Najla Nasr |
| author_sort | Jarrod York |
| collection | DOAJ |
| description | Although the advent of ART has significantly reduced the morbidity and mortality associated with HIV infection, the stable pool of HIV in latently infected cells requires lifelong treatment adherence, with the cessation of ART resulting in rapid reactivation of the virus and productive HIV infection. Therefore, these few cells containing replication-competent HIV, known as the latent HIV reservoir, act as the main barrier to immune clearance and HIV cure. While several strategies involving HIV silencing or its reactivation in latently infected cells for elimination by immune responses have been explored, exciting cell based immune therapies involving genetically engineered T cells expressing synthetic chimeric receptors (CAR T cells) are highly appealing and promising. CAR T cells, in contrast to endogenous cytotoxic T cells, can function independently of MHC to target HIV-infected cells, are efficacious and have demonstrated acceptable safety profiles and long-term persistence in peripheral blood. In this review, we present a comprehensive picture of the current efforts to target the HIV latent reservoir, with a focus on CAR T cell therapies. We highlight the current challenges and advances in this field, while discussing the importance of novel CAR designs in the efforts to find a HIV cure. |
| first_indexed | 2024-04-13T07:37:16Z |
| format | Article |
| id | doaj.art-a1af93c7662f4220b662764d9663f40f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T07:37:16Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a1af93c7662f4220b662764d9663f40f2022-12-22T02:56:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-04-011310.3389/fimmu.2022.873701873701Evolving Strategies to Eliminate the CD4 T Cells HIV Viral Reservoir via CAR T Cell ImmunotherapyJarrod York0Jarrod York1Kavitha Gowrishankar2Kavitha Gowrishankar3Kavitha Gowrishankar4Kenneth Micklethwaite5Kenneth Micklethwaite6Kenneth Micklethwaite7Kenneth Micklethwaite8Sarah Palmer9Sarah Palmer10Anthony L. Cunningham11Anthony L. Cunningham12Najla Nasr13Najla Nasr14Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW, AustraliaCentre for Cancer Research, The Westmead Institute for Medical Research, Westmead, NSW, AustraliaCentre for Cancer Research, The Westmead Institute for Medical Research, Westmead, NSW, AustraliaChildren’s Cancer Research Unit, Kids Research, The Children’s Hospital at Westmead, Sydney Children’s Hospitals Network, Westmead, NSW, AustraliaFaculty of Medicine and Health, Sydney Institute for Infectious Diseases, School of Medical Sciences, The University of Sydney, Sydney, NSW, AustraliaCentre for Cancer Research, The Westmead Institute for Medical Research, Westmead, NSW, AustraliaFaculty of Medicine and Health, Sydney Institute for Infectious Diseases, School of Medical Sciences, The University of Sydney, Sydney, NSW, AustraliaBlood Transplant and Cell Therapies Program, Department of Haematology, Westmead Hospital, Sydney, NSW, AustraliaNSW Health Pathology Blood Transplant and Cell Therapies Laboratory – Institute of Clinical Pathology and Medical Research (ICPMR) Westmead, Sydney, NSW, AustraliaCentre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW, AustraliaFaculty of Medicine and Health, Sydney Institute for Infectious Diseases, School of Medical Sciences, The University of Sydney, Sydney, NSW, AustraliaCentre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW, AustraliaFaculty of Medicine and Health, Sydney Institute for Infectious Diseases, School of Medical Sciences, The University of Sydney, Sydney, NSW, AustraliaCentre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW, AustraliaFaculty of Medicine and Health, Sydney Institute for Infectious Diseases, School of Medical Sciences, The University of Sydney, Sydney, NSW, AustraliaAlthough the advent of ART has significantly reduced the morbidity and mortality associated with HIV infection, the stable pool of HIV in latently infected cells requires lifelong treatment adherence, with the cessation of ART resulting in rapid reactivation of the virus and productive HIV infection. Therefore, these few cells containing replication-competent HIV, known as the latent HIV reservoir, act as the main barrier to immune clearance and HIV cure. While several strategies involving HIV silencing or its reactivation in latently infected cells for elimination by immune responses have been explored, exciting cell based immune therapies involving genetically engineered T cells expressing synthetic chimeric receptors (CAR T cells) are highly appealing and promising. CAR T cells, in contrast to endogenous cytotoxic T cells, can function independently of MHC to target HIV-infected cells, are efficacious and have demonstrated acceptable safety profiles and long-term persistence in peripheral blood. In this review, we present a comprehensive picture of the current efforts to target the HIV latent reservoir, with a focus on CAR T cell therapies. We highlight the current challenges and advances in this field, while discussing the importance of novel CAR designs in the efforts to find a HIV cure.https://www.frontiersin.org/articles/10.3389/fimmu.2022.873701/fullHIV-1CD4CD8chimeric antigen receptorlatencyreactivation |
| spellingShingle | Jarrod York Jarrod York Kavitha Gowrishankar Kavitha Gowrishankar Kavitha Gowrishankar Kenneth Micklethwaite Kenneth Micklethwaite Kenneth Micklethwaite Kenneth Micklethwaite Sarah Palmer Sarah Palmer Anthony L. Cunningham Anthony L. Cunningham Najla Nasr Najla Nasr Evolving Strategies to Eliminate the CD4 T Cells HIV Viral Reservoir via CAR T Cell Immunotherapy Frontiers in Immunology HIV-1 CD4 CD8 chimeric antigen receptor latency reactivation |
| title | Evolving Strategies to Eliminate the CD4 T Cells HIV Viral Reservoir via CAR T Cell Immunotherapy |
| title_full | Evolving Strategies to Eliminate the CD4 T Cells HIV Viral Reservoir via CAR T Cell Immunotherapy |
| title_fullStr | Evolving Strategies to Eliminate the CD4 T Cells HIV Viral Reservoir via CAR T Cell Immunotherapy |
| title_full_unstemmed | Evolving Strategies to Eliminate the CD4 T Cells HIV Viral Reservoir via CAR T Cell Immunotherapy |
| title_short | Evolving Strategies to Eliminate the CD4 T Cells HIV Viral Reservoir via CAR T Cell Immunotherapy |
| title_sort | evolving strategies to eliminate the cd4 t cells hiv viral reservoir via car t cell immunotherapy |
| topic | HIV-1 CD4 CD8 chimeric antigen receptor latency reactivation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.873701/full |
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