Increased cellular avidity upon combining multi-targeting and co-stimulation leads to enhanced CAR-T cell sensitivity and persistence
18 Jun 2021

Clinical studies of CAR-T cell therapy have established that mechanisms of treatment failure include the downregulation of target antigen expression and the limited persistence of effective CAR-T cells. In this webinar, Dr. Maria Themeli, Group Leader at the Department of Hematology Amsterdam UMC, will demonstrate how co-targeting mediated by a CAR and a costimulatory chimeric receptor (CCR) can enhance anti-tumor CAR-T cell performance by:

  • increasing synaptic cell avidity and killing capacity
  • conferring increased persistence through the incorporation of complementary co-stimulation combining 4-1BB and CD28

Themeli’s findings show that, concomitant engagement of CD38 by a high-affinity CCR enhanced the anti-tumor responses of BCMA and CD19 CAR-T cells by increasing cytotoxicity, cytokine secretion, expansion, and persistence. Most importantly, the improved properties of CAR+CCR T cells enabled the lysis and in vivo eradication of antigen-low tumor clones resistant to conventional CAR-T cells.

Multiplexing targeting and co-stimulation through the CAR+CCR combination is a powerful strategy to boost the immunotherapeutic potential of engineered T cells. In this webinar, we introduce a new technology, the z-Movi® Cell Avidity Analyzer, for rapidly screening and selecting the right candidates using this novel approach. Cell avidity measurements allows us to observe increased cellular avidity when comparing the CAR+CCR setting to a single CAR targeting BCMA. Most notably, the avidity data is able to predict the observed in vivo findings. Therefore, this novel opportunity of pre-screening of lead CAR products could accelerate the bench-to-bed trajectory significantly.

Key learning objectives

  • New strategies to boost immunotherapeutic potential of engineered T cells via multiplexing targeting and co-stimulation
  • How cellular avidity measurements can be used to rapidly screen and select the right candidates
  • Why avidity can serve as a predictor of increased efficacy of CAR T cell products

Who should attend?

Anyone with a strong interest in developing new immunotherapies against cancer using bispecific antibodies, CAR-T cells, NK cells, TCR T cells, allogeneic T cells, or other similar strategies.