Engineered calcium-regulated affinity protein for efficient internalization and lysosomal toxin delivery.

ABSTRACT: The emerging strategy of protein-drug conjugates (PDCs) for targeted cancer therapy holds great potential to improve treatment efficacy by specifically targeting cancer biomarkers and delivering toxic payloads directly to tumor cells, minimizing off-target toxicity. The success of this approach depends on the internalization and retention of the payload in target cells. This study introduces a method using a small protein domain engineered for conditional target affinity, enabling lysosomal trafficking independent of the biological fate of the receptor. Specifically, we describe the development of an EGF receptor binder, CaRA_EGFR, with calcium-regulated affinity (CaRA), meaning the target binding strength is tailored by the available calcium concentration. This allows for endoso

SUBMITTER: Jonsson M 

PROVIDER: S-EPMC12685030 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature