Article
作者: Umuhoza, Saluwa  ; Scharenberg, Andrew M.  ; Mangio, Richard S.  ; Hernandez Lopez, Susana A.  ; Qin, Jim  ; Shin, Seungjin  ; Gottschalk, Rebecca J.  ; Michels, Kathryn R.  ; Parrilla, Don  ; Kiem, Hans-Peter  ; Park, Lisa Y.  ; Tang, Weiliang  ; Cooper, Sara E.  ; Parker, Maura H.  ; McDonnell, Mollie M.  ; Beitz, Laurie O.  ; Ulrich-Lewis, Justin T.  ; Ericson, Nolan G.  ; Leung, Wai-Hang  ; Nicolai, Christopher J.  ; Ryu, Byoung Y.  ; Brandes, Alissa H.  ; Larson, Ryan P. 
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.