uu.seUppsala universitets publikasjoner
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Vaccines targeting self-antigens: mechanisms and efficacy-determining parameters
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
Vise andre og tillknytning
2015 (engelsk)Inngår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 29, nr 8, s. 3253-3262Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

We recently showed that it is possible to compromise tumor vessel function and, as a consequence, suppress growth of aggressive preclinical tumors by immunizing against the tumor vascular markers extra domain-A (ED-A) or -B (ED-B) of fibronectin, using a fusion protein consisting of the ED-A or ED-B peptide fused to bacterial thioredoxin. To address the mechanism behind fusion protein-induced immunization and the specific contribution of the different vaccine constituents to elicit an anti-self-antibody response, we immunized mice with modified or unmodified self-antigens, combined with different adjuvant components, and analyzed antibody responses by ELISA in sera. Several essential requirements to circumvent tolerance were identified: (1) a potent pattern recognition receptor agonist like an oligonucleotide containing unmethylated cytosine and guanine dinucleotides (CpG); (2) a depot adjuvant to keep the CpG at the site of injection; and (3) the presence of foreign sequences in the vaccine protein. Lack of either of these factors abolished the anti-self-response (P = 0.008). In mice genetically deficient for type I IFN signaling, there was a 60% reduction in the anti-self-response compared with wildtype (P = 0.011), demonstrating a key role of this pathway in CpG-induced circumvention of self-tolerance. Identification of these mechanistic requirements to generate a potent anti-self-immune response should significantly aid the design of efficient, specific, and safe therapeutic cancer vaccines.

sted, utgiver, år, opplag, sider
2015. Vol. 29, nr 8, s. 3253-3262
Emneord [en]
cancer, ED-B of fibronectin, adjuvant, CpG, type I IFN
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-261251DOI: 10.1096/fj.15-271502ISI: 000358796900014PubMedID: 25868727OAI: oai:DiVA.org:uu-261251DiVA, id: diva2:850422
Forskningsfinansiär
Swedish Cancer SocietySwedish Research CouncilTilgjengelig fra: 2015-09-01 Laget: 2015-08-31 Sist oppdatert: 2017-12-04bibliografisk kontrollert

Open Access i DiVA

Fulltekst mangler i DiVA

Andre lenker

Forlagets fulltekstPubMed

Personposter BETA

Saupe, FalkFemel, JuliaCedervall, JessicaOlsson, Anna-Karin

Søk i DiVA

Av forfatter/redaktør
Saupe, FalkFemel, JuliaCedervall, JessicaOlsson, Anna-Karin
Av organisasjonen
I samme tidsskrift
The FASEB Journal

Søk utenfor DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 778 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf