Generation of tertiary lymphoid structures and CD3pos CD8pos CD56pos NKG2Dpos CAR TaNK cells following subcutaneous injection of CD3-directed lentiviral vector-loaded PBMC

Anirban Kundu, Dongming Zhang, Frederic Vigant, Junyi Zhang, Gregory Schreiber, Ewa Jaruga-Killeen, Alissa R Kerner, Michelle Andraza, Wei Zhang, John Henkelman, Renata Soares, Gregory I. Frost, & Sid P. Kerkar

Abstract #560

Key Messages:

  • Subcutaneous (SC) injection of peripheral blood mononuclear cells (PBMC) loaded for 4hrs with CD3-directed lentivector (LV) generate a novel CAR T and NK-like (TaNK) cell capable of enhanced proliferation and target elimination
  • Following SC administration, CAR expression and expansion initiates at the site of injection from tertiary lymphoid structures comprised of T cells, macrophages, and dendritic cells
  • CARpos cells formed subcutaneously effectively traffic to the tumor site within 2 weeks post-injection
  • From this novel LV CAR and Driver vector platform, CD19 or CD22 CARpos cells with a T and NK-like phenotype (CD3posCD8posCD56posNKG2Dpos) and unique cytokine profile, mediate target elimination with enhanced systemic proliferation and engraftment compared to traditional CD4/8 41BB CAR-Ts administered intravenously into a lymphoreplete animal model
  • Through a subcutaneous initiation from TLS, a rapid and scalable process for the development of a CAR-TaNK therapy with reduced cytokine impact and immunosuppression may be clinically feasible