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In vivo CAR T-cell generation in nonhuman primates using lentiviral vectors displaying a multidomain fusion ligand.
Nicolai, Christopher J; Parker, Maura H; Qin, Jim; Tang, Weiliang; Ulrich-Lewis, Justin T; Gottschalk, Rebecca J; Cooper, Sara E; Hernandez Lopez, Susana A; Parrilla, Don; Mangio, Richard S; Ericson, Nolan G; Brandes, Alissa H; Umuhoza, Saluwa; Michels, Kathryn R; McDonnell, Mollie M; Park, Lisa Y; Shin, Seungjin; Leung, Wai-Hang; Scharenberg, Andrew M; Kiem, Hans-Peter; Larson, Ryan P; Beitz, Laurie O; Ryu, Byoung Y.
Affiliation
  • 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.
Blood ; 144(9): 977-987, 2024 Aug 29.
Article in En | MEDLINE | ID: mdl-38861668
ABSTRACT
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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: T-Lymphocytes / Immunotherapy, Adoptive / Lentivirus / Receptors, Chimeric Antigen / Genetic Vectors Limits: Animals / Humans Language: En Journal: Blood Year: 2024 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: T-Lymphocytes / Immunotherapy, Adoptive / Lentivirus / Receptors, Chimeric Antigen / Genetic Vectors Limits: Animals / Humans Language: En Journal: Blood Year: 2024 Type: Article