1. Delivery route, MyD88 signaling and cross-priming events determine the anti-tumor efficacy of an adenovirus based melanoma vaccine
- Author
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Hangalapura, Basav N., Oosterhoff, Dinja, Gupta, Tarun, de Groot, Jan, Wijnands, Pepijn G.J.T.B., van Beusechem, Victor W., den Haan, Joke, Tüting, Thomas, van den Eertwegh, Alfons J.M., Curiel, David T., Scheper, Rik J., and de Gruijl, Tanja D.
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ANTINEOPLASTIC agents , *ADENOVIRUSES , *MELANOMA , *VIRAL vaccines , *IMMUNOTHERAPY , *COMPARATIVE studies , *LYMPH nodes , *ANTIGENS , *DRUG administration , *VACCINATION - Abstract
Abstract: Adenovirus (Ad)-based vaccines are considered for cancer immunotherapy, yet, detailed knowledge on their mechanism of action and optimal delivery route for anti-tumor efficacy is lacking. Here, we compared the anti-tumor efficacy of an Ad-based melanoma vaccine after intradermal, intravenous, intranasal or intraperitoneal delivery in the B16F10 melanoma model. The intradermal route induced superior systemic anti-melanoma immunity which was MyD88 signaling-dependent. Predominant transduction of non-professional antigen-presenting cells at the dermal vaccination sites and draining lymph nodes, suggested a role for cross-presentation, which was confirmed in vitro. We conclude that the dermis provides an optimal route of entry for Ad-based vaccines for high-efficacy systemic anti-tumor immunization and that this immunization likely involves cross-priming events in the draining lymph nodes. [Copyright &y& Elsevier]
- Published
- 2011
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