SGN-CD228A

SGN-CD228A is an investigational antibody-drug conjugate (ADC) targeting melanotransferrin (CD228, also known as MELTF or MFI2), a cell-surface protein highly expressed in several cancers including melanoma, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), colorectal cancer, and pancreatic cancer. The drug consists of a humanized IgG1 monoclonal antibody (hL49) with high specificity for CD228 that is stably conjugated to approximately eight molecules of the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a novel glucuronide linker. This design allows targeted delivery of MMAE to tumor cells expressing CD228, leading to internalization and subsequent cytotoxicity through inhibition of tubulin polymerization and induction of apoptosis. Preclinical studies demonstrated potent antitumor activity across multiple solid tumor models with heterogeneous antigen expression. Clinical development was pursued in advanced solid tumors; however, the program was discontinued due to insufficient antitumor activity and safety concerns related primarily to ocular toxicity, peripheral neuropathy, and neutropenia[1][2][3][4][5].