Induction of CAMEL/NY-ESO-ORF2-specific CD8+ T cells upon stimulation with dendritic cells infected with a modified Ad5 vector expressing a chimeric Ad5/35 fiber.
Delivery of the full-length tumor antigen might be more successful in immunotherapy than single peptides and has the advantage that patients no longer need to be selected for their HLA type. In this study, we tested the in vitro induction of CAMEL/NY-ESO-ORF2-specific T cells by dendritic cells infected with an adenovirus (Ad) type 5 vector containing the fiber shaft and knob of human serotype Ad35 (Ad5F35 vector). Our data show induction of CD8(+) T cells specific for the known HLA-A(*)0201-binding CAMEL/NY-ESO-ORF2(1-11) epitope by DC infected with Ad5F35-CAMEL, but not by DC pulsed with the recombinant CAMEL protein. In one healthy donor, even CD8(+) T cells specific for a new HLA-B7-binding CAMEL/NY-ESO-ORF2(46-54) epitope were raised. In conclusion, the in vitro induction of CAMEL/NY-ESO-ORF2-specific CD8(+) T cells in healthy donors by DC infected with Ad5F35-CAMEL strongly supports further investigation of the Ad5F35 vector as a vehicle for gene transfer into DC for the generation of tumor antigen-specific CD8(+) T cell responses in vivo.
Slager
Elisabeth H
EH
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
van der Minne
Caroline E
CE
Goudsmit
Jaap
J
van Oers
Johanna M M
JM
Kostense
Stefan
S
Havenga
Menzo J E
MJ
Osanto
Susanne
S
Griffioen
Marieke
M
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology*; D000954:Antigens, Surface; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D018604:Epitope Mapping; D015316:Genetic Therapy; D005822:Genetic Vectors; D015234:HLA-A Antigens / Q000378:metabolism; D015793:HLA-B7 Antigen / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology*; D009097:Multienzyme Complexes / Q000378:metabolism; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011993:Recombinant Fusion Proteins / Q000235:genetics
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C104948:CTAG1B protein, human; C510162:CTAG2 protein, human; D015234:HLA-A Antigens; D015793:HLA-B7 Antigen; D007378:Interleukins; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D010455:Peptides; D011993:Recombinant Fusion Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex