Guiding the killer and bringing in accomplices: bispecific antibody treatment for malignant melanoma
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2016-02-01Author
Szegezdi, Eva
Leverkus, Martin
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Szegezdi, Eva; Leverkus, Martin (2016). Guiding the killer and bringing in accomplices: bispecific antibody treatment for malignant melanoma. Journal of Investigative Dermatology 136 (2), 362-364
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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 Fcg-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 Fcg-receptor-carrying immune cells that can mount an immune response against the tumor cells.