Autologous antigen-presenting cells efficiently expand piggyBac transposon CAR-T cells with predominant memory phenotype
نویسندگان
چکیده
The quality of chimeric antigen receptor (CAR)-T cell products, including the expression memory and exhaustion markers, has been shown to influence their long-term functionality. manufacturing process CAR-T cells should be optimized prevent early T during expansion. Activation by monoclonal antibodies is a critical step for expansion, which may sometimes induce excess stimulation cells. Given that piggyBac transposon (PB)-based gene transfer could circumvent conventional pre-activation cells, we established method PB-mediated HER2-specific (PB-HER2-CAR-T cells) maintains phenotype without exhaustion. Through CAR-transduced with autologous peripheral blood mononuclear cell-derived feeder expressing both truncated HER2, CD80, 4-1BBL proteins, effectively propagate memory-rich, PD-1-negative PB-HER2-CAR-T demonstrated sustained antitumor efficacy in vitro debulked HER2-positive tumors vivo. Mice treated rejected second tumor establishment owing vivo expansion Our simple effective using PB system genetically modified donor-derived promising strategy use PB-CAR-T therapy.
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ژورنال
عنوان ژورنال: Molecular therapy. Methods & clinical development
سال: 2021
ISSN: ['2329-0501']
DOI: https://doi.org/10.1016/j.omtm.2021.03.011