嵌合抗原受体
体内
计算生物学
T细胞
转导(生物物理学)
生物
细胞
细胞生物学
病毒载体
癌症研究
免疫学
重组DNA
遗传学
免疫系统
基因
生物化学
作者
Christopher J. Nicolai,Maura H. Parker,Jim Qin,Weiliang Tang,Justin Theophilus Ulrich-Lewis,Rebecca Gottschalk,Sara Cooper,Susana López,Don Parrilla,Richard S. Mangio,Nolan G. Ericson,Alissa Brandes,Saluwa Umuhoza,Kathryn Michels,Mollie M. McDonnell,L. P. Park,Seungjin Shin,Wai‐Hang Leung,Andrew M. Scharenberg,Hans‐Peter Kiem,Ryan Larson,Laurie Beitz,Byoung Y. Ryu
出处
期刊:Blood
[American Society of Hematology]
日期:2024-06-11
标识
DOI:10.1182/blood.2024024523
摘要
Chimeric antigen receptor (CAR) T-cell therapies have demonstrated transformative efficacy in treating B-cell malignancies. However, high cost and manufacturing complexities hinder their widespread use. To overcome these hurdles, we have developed the VivoVecTM 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 VivoVecTM particles (VVPs) in the form of a multi-domain 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 non-human primates resulted in the robust generation of anti-CD20 CAR T-cells and the complete depletion of B cells for more than 10 weeks. These data validate the VivoVecTM 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.
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