title: Guiding the Killer and Bringing in Accomplices: Bispecific Antibody Treatment for Malignant Melanoma.
abstract: Discovery of oncogene and immune checkpoint targeting has transformed melanoma therapy in the last 5 years. However, treatment of primary or secondary drug-resistant melanoma remains a challenge. Agents designed to activate the cell death machinery directly, for example by activating the death receptors expressed by melanoma cells, could break drug resistance, and they may achieve long-lasting therapeutic success. He et al. report their studies of an MCSPxDR5 bispecific, tetravalent antibody that can simultaneously target death receptor 5 (DR5, TRAIL-R2) and melanoma-associated chondroitin sulfate proteoglycan (MCSP). This antibody can exert strong and selective DR5-dependent cytotoxic activity against MCSP-expressing melanoma cells. Crosslinking of the antibody with Fcγ-receptors increased the cytotoxic potential further, without compromising its selectivity. This approach offers a novel immunotherapeutic tool via coupling of three cooperating processes: delivering the death receptor agonist to the malignant cell population, potent activation of DR5-mediated cell death signaling, and recruitment of Fcγ-receptor-carrying immune cells that can mount an immune response against the tumor cells.
authors.affiliation: Apoptosis Research Centre (ARC), School of Natural Sciences, National University of Ireland, Galway, Biosciences, Dangan, Galway, Ireland. Electronic address: eva.szegezdi@nuigalway.ie.
authors.forename: Eva
authors.initials: E
authors.lastname: Szegezdi
authors.affiliation: Department of Dermatology and Allergology, Medical Faculty of the RWTH Aachen, Aachen, Germany. Electronic address: mleverkus@ukaachen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Leverkus
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D006801:Humans; D024101:Mitochondrial Proteins / Q000276:immunology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology*
chemical_list: D024101:Mitochondrial Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand