title: Delivery route, MyD88 signaling and cross-priming events determine the anti-tumor efficacy of an adenovirus based melanoma vaccine.
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.
authors.affiliation: Department of Medical Oncology, VU University Medical Center and Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Basav N
authors.initials: BN
authors.lastname: Hangalapura
authors.forename: Dinja
authors.initials: D
authors.lastname: Oosterhoff
authors.forename: Tarun
authors.initials: T
authors.lastname: Gupta
authors.forename: Jan
authors.initials: J
authors.lastname: de Groot
authors.forename: Pepijn G J T B
authors.initials: PG
authors.lastname: Wijnands
authors.forename: Victor W
authors.initials: VW
authors.lastname: van Beusechem
authors.forename: Joke
authors.initials: J
authors.lastname: den Haan
authors.forename: Thomas
authors.initials: T
authors.lastname: Tüting
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: van den Eertwegh
authors.forename: David T
authors.initials: DT
authors.lastname: Curiel
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology; D007271:Injections, Intradermal; D007275:Injections, Intravenous; D008198:Lymph Nodes / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*
chemical_list: D019496:Cancer Vaccines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88