Peer-Reviewed Journal Details
Mandatory Fields
Eva Szegezdi, Martin Levelrkus
2016
February
Journal Of Investigative Dermatology
Guiding the Killer and Bringing in Accomplices: Bispecific Antibody Treatment for Malignant Melanoma
Published
()
Optional Fields
136
2
362
364
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.
http://www.jidonline.org/article/S0022-202X(15)00093-7/abstract
http://dx.doi.org/10.1016/j.jid.2015.12.002
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