Covalent Proteins as Targeted Radionuclide Therapies Enhance Antitumor Effects.

ABSTRACT: Molecularly targeted radionuclide therapies (TRTs) struggle with balancing efficacy and safety, as current strategies to increase tumor absorption often alter drug pharmacokinetics to prolong circulation and normal tissue irradiation. Here we report the first covalent protein TRT, which, through reacting with the target irreversibly, increases radioactive dose to the tumor without altering the drug's pharmacokinetic profile or normal tissue biodistribution. Through genetic code expansion, we engineered a latent bioreactive amino acid into a nanobody, which binds to its target protein and forms a covalent linkage via the proximity-enabled reactivity, cross-linking the target irreversibly in vitro, on cancer cells, and on tumors in vivo. The radiolabeled covalent nanobody marke

SUBMITTER: Klauser PC 

PROVIDER: S-EPMC10311652 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature