CURRENT ACCREDITATIONS
CAR-T Discovery Challenge
Relapse after Chimeric Antigen Receptor (CAR) T-cell therapy occurs in roughly 50% to 60% of patients. This is primarily driven by the inability of modified cells to persist over time, functional exhaustion, and the ability of cancer cells to hide or change their targeted receptors (antigen escape)
The Solution: B Cell malignancies are used to generate subtypes carrying heterogenous antigen density. Activated naïve B cells diversify into specialized cell types to effectively target pathogens. This diversification is used to generate a clonal evolution in vitro before transfering each clonal sub type into fish.
CD19 Negative Clonal Evolution in Zebrafish
Customized Screening System
Heterogenous subtype carrying fish are screened for efficacy and relapse
Outcomes: High-throughput screening of entire compound libraries identified a 3% hit rate of molecules resistant to clonal heterogeneity. These candidates underwent secondary screening to eliminate those with chronic toxicity and undesired off-target effects, narrowing the pool to the top four compounds. Finally, these four leads were evaluated for optimal pharmacokinetic (PK) profiles and structurally optimized prior to advancing to further development phases.
