In vivo delivery of CD3-directed CD19-CAR lentivectors leads to the generation of CAR-T and NK-like (CAR-TaNK) cells capable of complete ablation of B cells in the blood, bone marrow, and tissue in NSG-SGM3 CD34+ humanized mice

Frederic Vigant, Ani Kundu, Ramya Yarlagadda, Cody Gowan, Michael Betts, Jonathan Kato, Renata Soares, Alan Ponce, Lintao Liu, Junyi Zhang, Dongming Zhang Ewa Jaruga-Killeen, Michelle Andraza, Suraj Kachgal, Gregory Schreiber, Wei Zhang, Gregory Wade, Gregory I. Frost, & Sid P. Kerkar

Key Points:

  • In vivo delivery of a CD3-directed lentivector that encodes a CD19 CAR leads to the generation of CAR+ cells with a T and NK (TaNK)-like phenotype
  • The newly generated CAR-TaNK cells are capable of eliminating CD19 B cells in a dose dependent manner, relative to the amount of lentivector delivered.
  • Mice injected with the lentivector also displayed reduced levels of inflammation in the liver and colon, suggesting possible application in autoimmune indications
  • The GCAR in vivo lentivector delivery platform represents a promising platform that can lead towards a true off-the-shelf CAR-T therapy