Expression of aberrantly glycosylated tumor mucin-1 on human DC after transduction with a fiber-modified adenoviral vector.
BACKGROUND
DC-presenting tumor Ag are currently being developed to be used as a vaccine in human cancer immunotherapy. To increase chances for successful therapy it is important to deliver full-length tumor Ag instead of loading single peptides.


METHODS
In this study we used a fiber-modified adenoviral vector (rAd5F35) containing full-length tumor Ag cDNA to transduce human monocyte (Mo)-derived DC in vitro. Cells were efficiently transduced and survived for at least 3 days after adenoviral transduction. Phenotype and function after maturation of Mo-DC were not impaired by infection with adenovirus particles. Expression of the tumor-associated Ag mucin-1 (MUC1) was detected using MAb defining different MUC1 glycoforms.


RESULTS
Non-transduced mature Mo-DC express endogenous MUC1 with normal glycosylation. After transduction with the rAd5F35-MUC1 adenoviral vector, Mo-DC also expressed MUC1 with tumor-associated glycosylation (Tn and T glycoforms), although no changes in mRNA levels of relevant glycosyltransferases could be demonstrated.


CONCLUSIONS
The presence of aberrantly glycosylated MUC1 may influence Ag presentation of the tumor glycoforms of MUC1 to immune cells, affecting tumor cell killing. These findings could be highly relevant to developing strategies for cancer immunotherapy based on DC vaccines using MUC1 as tumor Ag.
van Leeuwen
E B M
EB
Department of Internal Medicine, Division of Hemato-Oncology, University Hospital Maastricht, Maastricht, The Netherlands.
Cloosen
S
S
Senden-Gijsbers
B L M G
BL
Agervig Tarp
M
M
Mandel
U
U
Clausen
H
H
Havenga
M J E
MJ
Duffour
M-T
MT
García-Vallejo
J J
JJ
Germeraad
W T V
WT
Bos
G M J
GM
D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005434:Flow Cytometry; D005822:Genetic Vectors; D006031:Glycosylation; D006801:Humans; D018396:Mucin-1; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; D012333:RNA, Messenger; D012799:Sialyltransferases