Targeting a Radiosensitizing Antibody-Drug Conjugate to a Radiation-Inducible Antigen.

ABSTRACT:

Purpose

We recently discovered that anti-TIP1 antibody activates endocytosis in cancer cells, which facilitates retention of antibody and dissociation of a conjugated drug. To improve the pharmacokinetics and cancer specificity of radiosensitizing drugs, we utilized antibody-drug conjugates (ADCs) that bind specifically to radiation-inducible antigen, TIP1, on non-small cell lung cancer (NSCLC). This approach exploits the long circulation time of antibodies to deliver a radiosensitizing drug to cancer each day during radiotherapy.

Experimental design

Antibodies to TIP1 were prioritized based on affinity, cancer-specific binding, and internalization. The lead antibody, 7H5, was conjugated with a cytotoxic drug MMAE because of its ability to radiosensitize cancer. Cytotoxicity

SUBMITTER: Lewis CD 

PROVIDER: S-EPMC9167454 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature