Definition

An antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody against human inactive tyrosine-protein kinase 7 (protein tyrosine kinase 7; PTK7) linked to LD343, which is comprised of a protease-cleavable hydrophilic linker conjugated to the microtubule-disrupting cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration of anti-PTK7/MMAE ADC PRO1107, the anti-PTK7 antibody moiety targets and binds to PTK7 expressed on tumor cells. Upon binding, internalization and cleavage, MMAE is released and binds to tubulin, and inhibits microtubule polymerization. This results in G2/M phase cell cycle arrest and apoptosis in PTK7-expressing tumor cells. In addition, this may cause a bystander effect, thereby further killing PTK7-expressing tumor cells. PTK7, a tumor-associated antigen (TAA), is overexpressed on a variety of cancer cells with limited expression in normal tissues. It is an integral player in cancer cell stemness and tumor progression. The highly hydrophilic stable, cleavable linker is used to mask the hydrophobicity of conjugated MMAE.