Subcutaneous injection of total nucleated cells rapidly isolated following four-hour peripheral whole blood exposure to CD3-directed CAR-T lentiviruses with a synthetic driver results in robust CAR-T proliferation and anti-tumor immunity

Dongming Zhang, Frederic Vigant, Qun He, Anirban Kundu, Wei Zhang, Hongliang Zong, Ewa Jaruga-Killeen, John Henkelman, Gregory Schreiber, Michelle Andraza, Alissa R Kerner, Gregory I Frost, & Sid P Kerkar

Abstract #1511

Key Messages

  • Here we describe a novel approach for the rapid isolation of total nucleated cells (TNC) reverse eluted off a leukocyte reduction filter from whole blood exposed for four hours to CD3-directed CAR-T Lentiviruses (LV)
  • CD3-directed CAR-T LVs induce TCR internalization (CD3 Dimming) in T cells including Naïve and Naïve-derived T cells present within the isolated TNCs, and mediate in vitro T cell growth, transgene expression, and function
  • Following subcutaneous injection (SC) of TNC, in vivo expansion of CAR-T cells first occurs locally at the site of injection and then expands into the systemic circulation and distal tumor sites
  • Subcutaneous (SC) injections of CD19 CAR-T LV-loaded TNCs induced significant anti-tumor immunity equivalent to CD19 CAR-T LV-loaded PBMCs isolated from whole blood
  • By leveraging this technology, we can develop a rapid, scalable, and cost-effective process for the development of a rapid point-of-care (rPOC) subcutaneous CAR-T therapy