Discovery, Engineering and Optimization of a Bispecific T-Cell Engager Against a Novel Low Copy Number Tumor Antigen
- Discovery of the novel tumor antigen, focusing on the identification strategies used to validate its high tumor selectivity and the challenges associated with targeting a protein with such a low-copy-number expression profile
- Rational engineering of the bispecific scaffold, detailing the optimization of the CD3 and tumor-binding domains to ensure a stable immunological synapse can form even when target density is minimal
- Optimization of the therapeutic window, highlighting how binding affinities were fine-tuned to maximize T-cell mediated killing of tumor cells while mitigating the risks of off-tumor toxicity and systemic cytokine release.