Contextual reprogramming of CAR-T cells for the treatment of HER2-expressing cancers.
11 AM GMT, 2 PM SGT, 10 AM PDT
Zhifen Yang joined Refuge Bio in 2017. She is currently the director of RnD at Refuge Bio, and her group leads preclinical development of Refuge CAR-T cells designed to target solid tumor malignancies. Her research is intensely focused on the mechanism of action and optimization of CRISPR/Cas9 and applying a “dead Cas9” (dCas9) to conditionally regulate the transcription of genes in response to antigen-specific CAR-T activation to increase CAR-T cells’ stemness and effectiveness. She obtained her Ph.D. in Cell Biology from University of Michigan, Ann Arbor.
BACKGROUND – Combining checkpoint inhibition (CPI) to adoptive cell therapy (ACT) may prevent engineered chimeric antigen receptor (CAR)-T cell exhaustion and improve outcomes. However, cumulative toxicities and costs limit this approach. In this webinar, we present a conditional, antigen encounter-dependent CRISPR interference (CRISPRi)-modulation circuit (RB-340-1) that promotes CAR-T resilience to checkpoint suppression, extending in vivo persistence and effectiveness. RB-340-1 consistently induced a higher production of homeostatic cytokines such as IL-2, resulting in significantly enhanced proliferation in vitro. This resulted in vivo in significantly superior suppression of growth of HER2+ FADU oropharyngeal cancer xenografts upon intra-tumoral and systemic administration and prolonged persistence of CAR-T cells.