In vivo generation of tumor-metabolism-regulated HER2-specific CAR+ cells eradicate established HER2+ gastric carcinomas with the novel subcutaneous route of administration of CD3-directed lentivector-loaded lymphocytes.

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

Key points:
  • Subcutaneous injection of tumor microenvironment-regulated HER2 CAR lentivector-loaded lymphocytes results in the robust, in vivo proliferation of CAR+ cells that exhibit anti-tumor activity against HER2+ gastric carcinomas.
  • Lymphocyte-specific fusion, internalization, and initiation of T cell activation are observed within four hours of exposure of lymphocytes to CD3-directed lentivector
  • Rapid manufacturing process represents a cost-effective approach for cellular immunotherapy