Endowing universal CAR T-cell with immune-evasive properties using TALEN-gene editing

• DOI: 10.1038/s41467-022-30896-2
• Publication Date: 2022-06-30T10:03:34Z
• Authors: Sumin Jo; Shipra Das; Alan Williams; Anne-Sophie Chretien; Thomas Pagliardini; Aude Le Roy; Jorge Postigo Fer...; Diane Le Clerre; Billal Jahangiri; Isabelle Chion-So...; Sandra Rozlan; Emilie Dessez; Agnes Gouble; Mathilde Dusséaux; Roman Galetto; Aymeric Duclert; Emanuela Marcenaro; Raynier Devillier; Daniel Olive; Philippe Duchateau; Laurent Poirot; Julien Valton
• Keywords: Cancer Immunotherapy

Universal CAR T-cell therapies are poised to revolutionize cancer treatment and improve patient outcomes. However, realizing these advantages in an allogeneic setting requires universal T-cells that can kill target tumor cells, avoid depletion by the host immune system, proliferate without attacking tissues. Here, we describe development of a novel immune-evasive scaffold using precise TALEN-mediated gene editing DNA matrices vectorized recombinant adeno-associated virus 6. We simultaneously disrupt repurpose endogenous TRAC B2M loci generate TCRαβ- HLA-ABC-deficient expressing construct NK-inhibitor named HLA-E. This highly efficient process enables engineered evade NK cell alloresponsive attacks extend their persistence antitumor activity presence cytotoxic levels vivo vitro, respectively. could enable broad use settings holds great promise for clinical applications.