Login / Signup

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

Christopher J NicolaiMaura H ParkerJim QinWeiliang TangJustin T Ulrich-LewisRebecca J GottschalkSara E CooperSusana A Hernandez LopezDon ParrillaRichard S MangioNolan G EricsonAlissa H BrandesSaluwa UmuhozaKathryn R MichelsMollie M McDonnellLisa Y ParkSeungjin ShinWai-Hang LeungAndrew M ScharenbergHans-Peter KiemRyan P LarsonLaurie O BeitzByoung Y Ryu
Published in: Blood (2024)
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.
Keyphrases
  • gene therapy
  • endothelial cells
  • high throughput
  • single cell
  • cell therapy
  • squamous cell carcinoma
  • rectal cancer