| Autor: |
Min Guan, Laura Lim, Leo Holguin, Tianxu Han, Vibhuti Vyas, Ryan Urak, Aaron Miller, Diana L. Browning, Liliana Echavarria, Shasha Li, Shirley Li, Wen-Chung Chang, Tristan Scott, Paul Yazaki, Kevin V. Morris, Angelo A. Cardoso, M. Suzette Blanchard, Virginia Le Verche, Stephen J. Forman, John A. Zaia, John C. Burnett, Xiuli Wang |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Methods & Clinical Development, Vol 25, Iss , Pp 344-359 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2329-0501 |
| DOI: |
10.1016/j.omtm.2022.04.007 |
| Popis: |
T cells engineered to express HIV-specific chimeric antigen receptors (CARs) represent a promising strategy to clear HIV-infected cells, but to date have not achieved clinical benefits. A likely hurdle is the limited T cell activation and persistence when HIV antigenemia is low, particularly during antiretroviral therapy (ART). To overcome this issue, we propose to use a cytomegalovirus (CMV) vaccine to stimulate CMV-specific T cells that express CARs directed against the HIV-1 envelope protein gp120. In this study, we use a GMP-compliant platform to engineer CMV-specific T cells to express a second-generation CAR derived from the N6 broadly neutralizing antibody, one of the broadest anti-gp120 neutralizing antibodies. These CMV-HIV CAR T cells exhibit dual effector functions upon in vitro stimulation through their endogenous CMV-specific T cell receptors or the introduced CARs. Using a humanized HIV mouse model, we show that CMV vaccination during ART accelerates CMV-HIV CAR T cell expansion in the peripheral blood and that higher numbers of CMV-HIV CAR T cells were associated with a better control of HIV viral load and fewer HIV antigen p24+ cells in the bone marrow upon ART interruption. Collectively, these data support the clinical development of CMV-HIV CAR T cells in combination with a CMV vaccine in HIV-infected individuals. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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