Anti-TRAILR2 antibody-toxin-conjugate and pharmaceutical use thereof in anti-tumor therapy

摘要

Provided is a broad-spectrum, efficient and anti-tumor anti-TRAILR2 antibody-toxin-conjugate (ADC, named Zapadcine-1(a, b, c, d) and Zapadcine-3(a, b, c, d, e)). Toxin with cytotoxic effect is linked to an anti-TRAILR2 humanized monoclonal antibody by means of a covalent bond by using disulfide bond bridging or conventional coupling technology and chemical linkers, so as to form an anti-TRAILR2 humanized antibody-toxin-conjugate. The ADC has the specificity of TRAILR2 positive tumors, and after conjugated to TRAILR2, the positive tumors can be endocytosed into lysosomes of tumor cells, and is degraded by means of proteases inside the lysosomes to release free micromolecule urotoxins, so that different TRAILR2 positive tumor cells are killed specifically, the tumor growth is suppressed, the tumor cells are even completely eliminated, and the tumor is cured.