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Structure-function analysis and therapeutic efficacy of antibodies to fungal melanin for melanoma radioimmunotherapy

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dc.creatornosanchuk, josh
dc.creatorRevskaya, E.
dc.creatorJiang, Z.
dc.creatorBryan, R. A.
dc.creatorJiao, R.
dc.creatorMalo, M. E.
dc.creatorGómez, B. L.
dc.creatorMorgenstern, A.
dc.creatorBruchertseifer, F.
dc.creatorRickles, D.
dc.creatorThornton, G. B.
dc.creatorBowen, A.
dc.creatorCasadevall, A.
dc.creatorDadachova, E.
dc.creator.googleNosanchuk, J.D.spa
dc.creator.googleJeyakumar, A.spa
dc.creator.googleRay, A.spa
dc.creator.googleRevskaya, E.spa
dc.creator.googleJiang, Z.spa
dc.creator.googleBryan, R.A.spa
dc.creator.googleAllen, K.J.H.spa
dc.creator.googleJiao, R.spa
dc.creator.googleMalo, M.E.spa
dc.creator.googleGómez, B.L.spa
dc.creator.googleMorgenstern, A.spa
dc.creator.googleBruchertseifer, F.spa
dc.creator.googleRickles, D.spa
dc.creator.googleThornton, G.B.spa
dc.creator.googleBowen, A.spa
dc.creator.googleCasadevall, A.spa
dc.creator.googleDadachova, E.spa
dc.date.accessioned2019-09-24T14:35:08Z
dc.date.available2019-09-24T14:35:08Z
dc.date.created2018
dc.date.issued2018
dc.description.abstractMetastatic melanoma remains difficult to treat despite recent approvals of several new drugs. Recently we reported encouraging results of Phase I clinical trial of radiolabeled with 188Re murine monoclonal IgM 6D2 to melanin in patients with Stage III/IV melanoma. Subsequently we generated a novel murine IgG 8C3 to melanin. IgGs are more amenable to humanization and cGMP (current Good Manufacturing Practice) manufacturing than IgMs. We performed comparative structural analysis of melanin-binding IgM 6D2 and IgG 8C3. The therapeutic efficacy of 213Bi- And 188Re-labeled 8C3 and its comparison with anti-CTLA4 immunotherapy was performed in B16-F10 murine melanoma model. The primary structures of these antibodies revealed significant homology, with the CDRs containing a high percentage of positively charged amino acids. The 8C3 model has a negatively charged binding surface and significant number of aromatic residues in its H3 domain, suggesting that hydrophobic interactions contribute to the antibody-melanin interaction. Radiolabeled IgG 8C3 showed significant therapeutic efficacy in murine melanoma, safety towards healthy melanin-containing tissues and favorable comparison with the anti-CTLA4 antibody. We have demonstrated that antibody binding to melanin relies on both charge and hydrophobic interactions while the in vivo data supports further development of 8C3 IgG as radioimmunotherapy reagent for metastatic melanoma. © 2018 The Author(s).eng
dc.format.mimetypeapplication/pdf
dc.identifier.doi10.1038/s41598-018-23889-z
dc.identifier.issn2045-2322
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/20323
dc.language.isoengspa
dc.relation.citationTitleScientific Reports
dc.relation.citationVolumeVol. 8
dc.relation.ispartofScientific Reports, ISSN:2045-2322, Vol. 8 (2018)spa
dc.relation.urihttps://www.nature.com/articles/s41598-018-23889-z.pdfspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.bibliographicCitationSkin Cancer - Melanoma, , http://www.cancer.org/cancer/skincancer-melanoma/detailedguide/melanoma-skin-cancer-key-statistics, American Cancer Society. 02/01/2016spa
dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subjectInteracciones hidrofóbicasspa
dc.subjectEficacia terapéuticaspa
dc.subjectMelanoma murinospa
dc.subject.ddcEnfermedadesspa
dc.subject.keywordComparison antictlaspa
dc.subject.keywordHydrophobic interactionsspa
dc.subject.keywordTherapeutic efficacyspa
dc.subject.keywordMurine Melanomaspa
dc.subject.lembNeoplasmasspa
dc.subject.lembMelanomaspa
dc.titleStructure-function analysis and therapeutic efficacy of antibodies to fungal melanin for melanoma radioimmunotherapyspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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