Pre-clinical data supporting immunotherapy for HIV using CMV-HIV-specific CAR T cells with CMV vaccine.

Autor:	Guan M; T Cell Therapeutics Research Laboratory, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA., Lim L; T Cell Therapeutics Research Laboratory, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA., Holguin L; Center for Gene Therapy, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Han T; Center for Gene Therapy, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Vyas V; T Cell Therapeutics Research Laboratory, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA., Urak R; Center for Gene Therapy, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Miller A; Department of Molecular Imaging and Therapy, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Browning DL; Center for Gene Therapy, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Echavarria L; Center for Gene Therapy, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Li S; Center for Gene Therapy, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Li S; Center for Gene Therapy, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Chang WC; T Cell Therapeutics Research Laboratory, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA., Scott T; Center for Gene Therapy, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Yazaki P; Department of Molecular Imaging and Therapy, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Morris KV; Center for Gene Therapy, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Cardoso AA; Center for Gene Therapy, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Blanchard MS; Division of Biostatistics, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Le Verche V; Center for Gene Therapy, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Forman SJ; T Cell Therapeutics Research Laboratory, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA., Zaia JA; Center for Gene Therapy, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Burnett JC; Center for Gene Therapy, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA., Wang X; T Cell Therapeutics Research Laboratory, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA.
Jazyk:	angličtina
Zdroj:	Molecular therapy. Methods & clinical development [Mol Ther Methods Clin Dev] 2022 Apr 13; Vol. 25, pp. 344-359. Date of Electronic Publication: 2022 Apr 13 (Print Publication: 2022).
DOI:	10.1016/j.omtm.2022.04.007
Abstrakt:	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. Competing Interests: Competing interests: A patent associated with this study covering the work has been held and submitted by City of Hope (US2016/024560) with X.W. and S.J.F. as inventors who could potentially receive licensing royalties in the future. The remaining authors declare no competing interests.
Databáze:	MEDLINE
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