Definition

An antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody against the tumor-associated antigen (TAA) receptor tyrosine kinase-like orphan receptor 1 (ROR1) site-specifically conjugated to a derivative of the highly potent anthracycline PNU-159682, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of NBE-002 targets and binds to ROR1 expressed on tumor cells. Upon binding and internalization, the anthracycline-based toxin intercalates into DNA and interacts with topoisomerase II. This leads to an inhibition of DNA replication and repair, and prevents RNA and protein synthesis. This kills the ROR1-expressing cancer cells. In addition, the PNU-159682 derivate may promote immunogenic cell death (ICD) and activate a cytotoxic T-lymphocyte (CTL)-mediated anti-tumor immune response, thereby further killing the ROR1-expressing tumor cells. ROR1, also known as neurotrophic tyrosine kinase, receptor-related 1 (NTRKR1), is expressed during embryogenesis and by certain leukemias. It plays key roles in tumor cell proliferation and survival.