Sökning: id:"swepub:oai:DiVA.org:uu-261251" >
Vaccines targeting ...
Vaccines targeting self-antigens : mechanisms and efficacy-determining parameters
-
- Saupe, Falk (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
-
- Huijbers, Elisabeth J. M. (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
-
Hein, Tobias (författare)
-
visa fler...
-
- Femel, Julia (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
-
- Cedervall, Jessica (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
-
- Olsson, Anna-Karin (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
-
Hellman, Lars (författare)
-
visa färre...
-
(creator_code:org_t)
- Wiley, 2015
- 2015
- Engelska.
-
Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 29:8, s. 3253-3262
- Relaterad länk:
-
https://urn.kb.se/re...
-
visa fler...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- cancer
- ED-B of fibronectin
- adjuvant
- CpG
- type I IFN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas