Differential Antitumor Effects of IgG and IgM Monoclonal Antibodies and Their Synthetic Complementarity-Determining Regions Directed to New Targets of B16F10-Nex2 Melanoma Cells

Página do item simplificado
dc.contributor.authorDobroff, Andrey Sergee Senos [UNIFESP]
dc.contributor.authorRodrigues, Elaine Guadalupe [UNIFESP]
dc.contributor.authorJuliano, Maria Aparecida [UNIFESP]
dc.contributor.authorFriaca, Dayson M.
dc.contributor.authorNakayasu, Ernesto S.
dc.contributor.authorAlmeida, Igor C
dc.contributor.authorMortara, Renato Arruda [UNIFESP]
dc.contributor.authorJacysyn, Jacqueline F.
dc.contributor.authorAmarante-Mendes, Gustavo P.
dc.contributor.authorMagliani, Walter
dc.contributor.authorConti, Stefania
dc.contributor.authorPolonelli, Luciano
dc.contributor.authorTravassos, Luiz Rodolpho [UNIFESP]
dc.contributor.institutionUniv Texas MD Anderson Canc Ctr
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniv Texas El Paso
dc.contributor.institutionUniv Parma
dc.date.accessioned2016-01-24T14:05:15Z
dc.date.available2016-01-24T14:05:15Z
dc.date.issued2010-08-01
dc.description.abstractMalignant melanoma has increased incidence worldwide and causes most skin cancer-related deaths. A few cell surface antigens that can be targets of antitumor immunotherapy have been characterized in melanoma. This is an expanding field because of the ineffectiveness of conventional cancer therapy for the metastatic form of melanoma. in the present work, antimelanoma monoclonal antibodies (mAbs) were raised against B16F10 cells (subclone Nex4, grown in murine serum), with novel specificities and antitumor effects in vitro and in vivo. MAb A4 (IgG2ak) recognizes a surface antigen on B16F10-Nex2 cells identified as protocadherin beta(13). It is cytotoxic in vitro and in vivo to B16F10-Nex2 cells as well as in vitro to human melanoma cell lines. MAb A4M (IgM) strongly reacted with nuclei of permeabilized murine tumor cells, recognizing histone 1. Although it is not cytotoxic in vitro, similarly with mAb A4, mAb A4M significantly reduced the number of lung nodules in mice challenged intravenously with B16F10-Nex2 cells. the V(H) CDR3 peptide from mAb A4 and V(L) CDR1 and CDR2 from mAb A4M showed significant cytotoxic activities in vitro, leading tumor cells to apoptosis. A cyclic peptide representing A4 CDR H3 competed with mAb A4 for binding to melanoma cells. MAb A4M CDRs L1 and L2 in addition to the antitumor effect also inhibited angiogenesis of human umbilical vein endothelial cells in vitro. As shown in the present work, mAbs A4 and A4M and selected CDR peptides are strong candidates to be developed as drugs for antitumor therapy for invasive melanoma.en
dc.description.affiliationUniv Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA
dc.description.affiliationUniversidade Federal de São Paulo, Expt Oncol Unit, Dept Microbiol, BR-04023062 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Div Parasitol, Dept Microbiol, BR-04023062 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Dept Pharmacol, Inst Biomed Sci, São Paulo, Brazil
dc.description.affiliationUniv Texas El Paso, Dept Biol Sci, Border Biomed Res Ctr, El Paso, TX 79968 USA
dc.description.affiliationUniv São Paulo, Immunol Invest Inst, Dept Immunol, Natl Inst Sci & Technol,Inst Biomed Sci, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Fac Med, Lab Med Invest, São Paulo, Brazil
dc.description.affiliationUniv Parma, Dept Pathol & Lab Med, Microbiol Sect, I-43100 Parma, Italy
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Expt Oncol Unit, Dept Microbiol, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Div Parasitol, Dept Microbiol, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipGraduate School, University of Texas at El Paso
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipIDNational Institutes of Health: 5G12RR008124
dc.format.extent204-217
dc.identifierhttp://dx.doi.org/10.1593/tlo.09316
dc.identifier.citationTranslational Oncology. Ann Arbor: Neoplasia Press, v. 3, n. 4, p. 204-217, 2010.
dc.identifier.doi10.1593/tlo.09316
dc.identifier.issn1936-5233
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32757
dc.identifier.wosWOS:000288495400001
dc.language.isoeng
dc.publisherNeoplasia Press
dc.relation.ispartofTranslational Oncology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleDifferential Antitumor Effects of IgG and IgM Monoclonal Antibodies and Their Synthetic Complementarity-Determining Regions Directed to New Targets of B16F10-Nex2 Melanoma Cellsen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Coleções
Em verificação - Geral