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Preclinical Development and Clinical-Scale Manufacturing of HIV Gag-Specific, LentivirusModified CD4 T Cells for HIV Functional Cure.


ABSTRACT: Activation, infection, and eventual depletion of human immunodeficiency virus (HIV)-specific cluster of differentiation 4 (CD4) T cells are the crucial pathogenetic events in acquired immunodeficiency syndrome (AIDS). We developed a cell and gene therapy to reconstitute HIV-specific CD4 T cells and prevent their destruction by HIV. Antigen-specific CD4 T cells will provide helper functions to support antiviral cytotoxic T lymphocyte (CTL) function and the production of virus-specific antibodies. However, ex vivo expansion of HIV-specific CD4 T cells is poor and previous gene therapies focused on bulk CD4 T cells without enriching for an antigen-specific subset. We developed a method for manufacturing autologous CD4+ T cell products highly enriched with Gag-specific T cells. Rare Gag-specific CD4 T cells in peripheral blood mononuclear cells (PBMCs) were increased nearly 1,000-fold by stimulating PBMC with Gag peptides, followed by depleting nontarget cells and transducing with lentivirus vector AGT103 to protect against HIV-mediated depletion and inhibit HIV release from latently infected cells. The average percentage of HIV-specific CD4 cells in the final products was 15.13%, and the average yield was 7 × 108 cells. The protocol for clinical-scale manufacturing of HIV-specific and HIV-resistant CD4 T cells is an important step toward effective immunotherapy for HIV disease.

SUBMITTER: Li H 

PROVIDER: S-EPMC7240062 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Preclinical Development and Clinical-Scale Manufacturing of HIV Gag-Specific, LentivirusModified CD4 T Cells for HIV Functional Cure.

Li Haishan H   Lahusen Tyler T   Xiao Lingzhi L   Muvarak Nidal N   Blazkova Jana J   Chun Tae-Wook TW   Pauza C David CD  

Molecular therapy. Methods & clinical development 20200503


Activation, infection, and eventual depletion of human immunodeficiency virus (HIV)-specific cluster of differentiation 4 (CD4) T cells are the crucial pathogenetic events in acquired immunodeficiency syndrome (AIDS). We developed a cell and gene therapy to reconstitute HIV-specific CD4 T cells and prevent their destruction by HIV. Antigen-specific CD4 T cells will provide helper functions to support antiviral cytotoxic T lymphocyte (CTL) function and the production of virus-specific antibodies.  ...[more]

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