Preventive DNA vaccination against CEA-expressing tumors with anti-idiotypic scFv6.C4 DNA in CEA-expressing transgenic mice

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dc.citation.issue3
dc.citation.volume66
dc.contributor.authorDenapoli, Priscila M. A. [UNIFESP]
dc.contributor.authorZanetti, Bianca F. [UNIFESP]
dc.contributor.authordos Santos, Adara A. [UNIFESP]
dc.contributor.authorde Moraes, Jane Z. [UNIFESP]
dc.contributor.authorHan, Sang W. [UNIFESP]
dc.coverageNew York
dc.date.accessioned2020-07-17T14:02:52Z
dc.date.available2020-07-17T14:02:52Z
dc.date.issued2017
dc.description.abstractCarcinoembryonic antigen (CEA) is expressed during embryonic life and in low level during adult life. Consequently, the CEA is recognized by the immune system as a self-antigen and thus CEA-expressing tumors are tolerated. Previously, we constructed a single chain variable fragment using the 6.C4 (scFv6.C4) hybridoma cell line, which gave rise to antibodies able to recognize CEA when C57/Bl6 mice were immunized. Here, the scFv6.C4 ability to prevent the CEA-expressing tumor growth was assessed in CEA-expressing transgenic mice CEA2682. CEA2682 mice immunized with the scFv6.C4 expressing plasmid vector (uP/PS-scFv6.C4) by electroporation gave rise to the CEA-specific AB3 antibody after the third immunization. Sera from immunized mice reacted with CEA-expressing human colorectal cell lines CO112, HCT-8, and LISP-1, as well as with murine melanoma B16F10 cells expressing CEA (B16F10-CEA). Cytotoxic T lymphocytes (CTL) from uP/PS-scFv6.C4 immunized mice lysed B16F10-CEA (56.7%) and B16F10 expressing scFv6.C4 (B16F10-scFv6.C4) (46.7%) cells, against CTL from uP-immunized mice (10%). After the last immunization, 5 x 10(5) B16F10-CEA cells were injected into the left flank. All mice immunized with the uP empty vector died within 40 days, but uP/PS-scFv6.C4 vaccinated mice (40%) remained free of tumor for more than 100 days. Splenocytes obtained from uP/PS-scFv6.C4 vaccinated mice showed higher T-cell proliferative activity than those from uP vaccinated mice. Collectively, DNA vaccination with the uP-PS/scFv6.C4 plasmid vector was able to give rise to specific humoral and cellular responses, which were sufficient to retard growth and/or eliminate the injected B16F10-CEA cells.en
dc.description.affiliationUniv Fed Sao Paulo, Res Ctr Gene Therapy, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biophys, BR-04044010 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Res Ctr Gene Therapy, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biophys, BR-04044010 Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFAPESP
dc.description.sponsorshipIDFAPESP: 2012/21861-1
dc.format.extent333-342
dc.identifierhttp://dx.doi.org/10.1007/s00262-016-1940-4
dc.identifier.citationCancer Immunology Immunotherapy. New York, v. 66, n. 3, p. 333-342, 2017.
dc.identifier.doi10.1007/s00262-016-1940-4
dc.identifier.issn0340-7004
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55064
dc.identifier.wosWOS:000394983800005
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofCancer Immunology Immunotherapy
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectDNA vaccineen
dc.subjectSingle-chain fragment variableen
dc.subjectAnti-idiotypic antibodyen
dc.subjectImmunological toleranceen
dc.subjectCarcinoembryonic antigenen
dc.subjectColorectal canceren
dc.titlePreventive DNA vaccination against CEA-expressing tumors with anti-idiotypic scFv6.C4 DNA in CEA-expressing transgenic miceen
dc.typeinfo:eu-repo/semantics/article
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