Complete cell-cell binding characterization

Researchers from the Dana-Farber Cancer Institute at Harvard Medical School have developed a cell avidity-based pre-clinical analysis pipeline for CAR selection. This innovative pipeline integrates both safety and potency assessments, utilizing the innovative LUMICKS’ Cell Avidity assays to evaluate a panel of CAR candidates for ccRCC. The Harvard-based team demonstrated a significant improvement with their newly developed G9 anti-CAIX CAR product, which offers potential advance in treatment options for kidney cancer patients. 

“Carbonic anhydrase IX (CAIX) was considered undruggable as it is expressed in both tumor and healthy tissues. Fine-tuning the cell avidity of the anti-CAIX chimeric antigen receptor (CAR) T cells ensures CAR-T only kills CAIX high tumor cells but not CAIX low cholangiocytes, thus mitigating the on-target off-tumor side effects.” 

Current short-term in vitro preclinical assays [1] fail to predict the poor APRIL-CAR performance in clinic; poor molecular binding was overlooked, and cellular binding was not assessed before continuation into clinical trials. Incorporating Cell Avidity analysis into the preclinical characterization of CAR T efficacy and safety, can improve the decision-making process and identify better candidates more robustly. 

The retrospective study, utilizing conventional in vitro assays such as cytokine secretion and cytotoxicity, revealed robust performance of the APRIL CAR-expressing cells, comparable to two analogous BCMA CARs approved by the FDA (bb2121 and LCAR) (Figure 1). 

“In this unique exploration of the reasons underpinning suboptimal clinical responses in the AUTO2 trial, the LUMICKS platform allowed us to establish poor tumor binding (or avidity) by cell bound APRIL compared to competitor CARs as a likely explanation. Only with such studies will the field acquire a greater understanding of the key preclinical readouts that can predict efficacy in patients.”