Rapid point-of-care subcutaneous CAR-T from blood draw to injection in 4 hours with modified LV encoding CARs and synthetic driver elements enables efficient CAR-T expansion and tumor regression - EXUMA Biotechnology

November 9 2020November 12, 2020 by EXUMA

Rapid point-of-care subcutaneous CAR-T from blood draw to injection in 4 hours with modified LV encoding CARs and synthetic driver elements enables efficient CAR-T expansion and tumor regression

Frederic Vigant, Qun He, Wei Zhang, Hongliang Zong, Anirban Kundu, Ewa Jaruga-Killeen, Gregory Schreiber, Michelle Andraza, Alissa Kerner, and Gregory I Frost

Abstract #117

Link to poster

Key Messages:

We demonstrate that subcutaneous (SC) delivery of human PBMCs modified by a 4- hour exposure to CD3-directed lentiviruses encoding a CD19 or a CD22 Chimeric Antigen Receptor (CAR) resulted in potent anti-tumor efficacy and robust in vivo expansion of CAR-T positive cells.

CAR-T cells driven by a synthetic domain identified from a high-throughput screening strategy exhibited > 10,000-fold expansion in vivo when given SC and demonstrated superior expansion compared to IV dosing.
A single dose of 1 million lentiviral modified PBMC given SC resulted in complete tumor regression in subcutaneous and disseminated Raji tumor models.

The entire process of genetic modification of PBMC and SC dosing can be completed in less than six hours, resulting in targeted genetic modification of T cells w/o prior activation. This represents a significant step forward for advancing rapid Point-of-Care (rPOC) CAR-T therapies.