Amphiphilic polyanhydride-based recombinant MUC4β-nanovaccine activates dendritic cells.
MUC4
cancer vaccine
immunotherapy
nanoparticle
pancreatic cancer
Journal
Genes & cancer
ISSN: 1947-6019
Titre abrégé: Genes Cancer
Pays: United States
ID NLM: 101516546
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
entrez:
2
7
2019
pubmed:
2
7
2019
medline:
2
7
2019
Statut:
ppublish
Résumé
Mucin 4 (MUC4) is a high molecular weight glycoprotein that is differentially overexpressed in pancreatic cancer (PC), functionally contributes to disease progression, and correlates with poor survival. Further, due to its aberrant glycosylation and extensive splicing, MUC4 is a potential target for cancer immunotherapy. Our previous studies have demonstrated the utility of amphiphilic polyanhydride nanoparticles as a useful platform for the development of protein-based prophylactic and therapeutic vaccines. In the present study, we encapsulated purified recombinant human MUC4-beta (MUC4β) protein in polyanhydride (20:80 CPTEG:CPH) nanoparticles (MUC4β-nanovaccine) and evaluated its ability to activate dendritic cells and induce adaptive immunity. Immature dendritic cells when pulsed with MUC4β-nanovaccine exhibited significant increase in the surface expressions of MHC I and MHC II and costimulatory molecules (CD80 and CD86), as well as, secretion of pro-inflammatory cytokines (IFN-γ, IL-6, and IL-12) as compared to cells exposed to MUC4β alone or MUC4β mixed with blank nanoparticles (MUC4β+NP). Following immunization, as compared to the other formulations, MUC4β-nanovaccine elicited higher IgG2b to IgG1 ratio of anti-MUC4β-antibodies suggesting a predominantly Th1-like class switching. Thus, our findings demonstrate MUC4β-nanovaccine as a novel platform for PC immunotherapy.
Identifiants
pubmed: 31258832
doi: 10.18632/genesandcancer.189
pii: 189
pmc: PMC6584211
doi:
Types de publication
Journal Article
Langues
eng
Pagination
52-62Subventions
Organisme : NCI NIH HHS
ID : U01 CA200466
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA195586
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA213862
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA127297
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA223429
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA036727
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA133774
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA183459
Pays : United States
Organisme : NIAAA NIH HHS
ID : R21 AA026428
Pays : United States
Déclaration de conflit d'intérêts
CONFLICT OF INTEREST Authors declare no conflict of interest.
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