Original Article
Cancer Gene Therapy (2004) 11, 227–236. doi:10.1038/sj.cgt.7700674 Published online 16 January 2004
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
Elisabeth H Slager1, Caroline E van der Minne1, Jaap Goudsmit2, Johanna M M van Oers1, Stefan Kostense2, Menzo J E Havenga2, Susanne Osanto1 and Marieke Griffioen1
- 1Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
- 2Crucell Holland BV, PO Box 2048, 2301 CA Leiden, The Netherlands
Correspondence: Dr Marieke Griffioen, PhD, Department of Clinical Oncology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: m.griffioen@lumc.nl
Received 27 June 2003; Published online 16 January 2004.
Abstract
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-ORF21–11 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-ORF246–54 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.
Keywords:
recombinant adenovirus, dendritic cells, T lymphocytes, melanoma, immunotherapy
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