Guiding the Killer and Bringing in Accomplices: Bispecific Antibody Treatment for Malignant Melanoma.
| Autor: | Szegezdi E; Apoptosis Research Centre (ARC), School of Natural Sciences, National University of Ireland, Galway, Biosciences, Dangan, Galway, Ireland. Electronic address: eva.szegezdi@nuigalway.ie., Leverkus M; Department of Dermatology and Allergology, Medical Faculty of the RWTH Aachen, Aachen, Germany. Electronic address: mleverkus@ukaachen.de. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of investigative dermatology [J Invest Dermatol] 2016 Feb; Vol. 136 (2), pp. 362-364. |
| DOI: | 10.1016/j.jid.2015.12.002 |
| Abstrakt: | 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. (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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