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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

Cancer Gene Therapy volume 11, pages 227–236 (2004)Cite this article

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.

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Acknowledgements

We thank A Zakhartchouk for cloning the measles antigen into Ad vectors and subsequent generation and in vitro testing of recombinant viruses carrying CAMEL antigen. We also thank B Vogelstein for providing the plasmids required for generation of the Ad5 vectors and RC Hoeben for propagating the Ad5 vectors encoding LAGE-1 and NY-ESO-1 on PER.C6TM. CAM van Bergen and JHF Falkenburg are gratefully acknowledged for in vitro experiments with purified proteasomes.

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Authors and Affiliations

  1. Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands

    Elisabeth H Slager, Caroline E van der Minne, Johanna M M van Oers, Susanne Osanto & Marieke Griffioen

  2. Crucell Holland BV, PO Box 2048, Leiden, 2301 CA, The Netherlands

    Jaap Goudsmit, Stefan Kostense & Menzo J E Havenga

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  1. Elisabeth H Slager
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Correspondence to Marieke Griffioen.

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Slager, E., van der Minne, C., Goudsmit, J. et al. 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. Cancer Gene Ther 11, 227–236 (2004). https://doi.org/10.1038/sj.cgt.7700674

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