In vivo CAR T-cell generation in nonhuman primates using lentiviral vectors displaying a multidomain fusion ligand.

Autor:	Nicolai CJ; Umoja Biopharma, Seattle, WA., Parker MH; Umoja Biopharma, Seattle, WA., Qin J; Umoja Biopharma, Seattle, WA., Tang W; Umoja Biopharma, Seattle, WA., Ulrich-Lewis JT; Umoja Biopharma, Seattle, WA., Gottschalk RJ; Umoja Biopharma, Seattle, WA., Cooper SE; Umoja Biopharma, Seattle, WA., Hernandez Lopez SA; Umoja Biopharma, Seattle, WA., Parrilla D; Umoja Biopharma, Seattle, WA., Mangio RS; Umoja Biopharma, Seattle, WA., Ericson NG; Umoja Biopharma, Seattle, WA., Brandes AH; Umoja Biopharma, Seattle, WA., Umuhoza S; Umoja Biopharma, Seattle, WA., Michels KR; Umoja Biopharma, Seattle, WA., McDonnell MM; Umoja Biopharma, Seattle, WA., Park LY; Umoja Biopharma, Seattle, WA., Shin S; Umoja Biopharma, Seattle, WA., Leung WH; Umoja Biopharma, Seattle, WA., Scharenberg AM; Umoja Biopharma, Seattle, WA., Kiem HP; Fred Hutchinson Cancer Center, Seattle, WA., Larson RP; Umoja Biopharma, Seattle, WA., Beitz LO; Umoja Biopharma, Seattle, WA., Ryu BY; Umoja Biopharma, Seattle, WA.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 Aug 29; Vol. 144 (9), pp. 977-987.
DOI:	10.1182/blood.2024024523
Abstrakt:	Abstract: Chimeric antigen receptor (CAR) T-cell therapies have demonstrated transformative efficacy in treating B-cell malignancies. However, high costs and manufacturing complexities hinder their widespread use. To overcome these hurdles, we have developed the VivoVec platform, a lentiviral vector capable of generating CAR T cells in vivo. Here, we describe the incorporation of T-cell activation and costimulatory signals onto the surface of VivoVec particles (VVPs) in the form of a multidomain fusion protein and show enhanced in vivo transduction and improved CAR T-cell antitumor functionality. Furthermore, in the absence of lymphodepleting chemotherapy, administration of VVPs into nonhuman primates resulted in the robust generation of anti-CD20 CAR T cells and the complete depletion of B cells for >10 weeks. These data validate the VivoVec platform in a translationally relevant model and support its transition into human clinical testing, offering a paradigm shift in the field of CAR T-cell therapies. (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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