Journal
VACCINE
Volume 29, Issue 12, Pages 2313-2321Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2011.01.022
Keywords
Adenovirus; Administration route; Melanoma
Categories
Funding
- Dutch Cancer Society [VU2005-3284]
- Netherlands Organization for Scientific Research [917-56-32]
- Stichting Avanti-STR
- NIH [5R01CA113454]
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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. (C) 2011 Elsevier Ltd. All rights reserved.
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