TY - JOUR
T1 - Delivery route, MyD88 signaling and cross-priming events determine the anti-tumor efficacy of an adenovirus based melanoma vaccine
AU - Hangalapura, Basav N.
AU - Oosterhoff, Dinja
AU - Gupta, Tarun
AU - de Groot, Jan
AU - Wijnands, Pepijn G.J.T.B.
AU - van Beusechem, Victor W.
AU - den Haan, Joke
AU - TÜting, Thomas
AU - van den Eertwegh, Alfons J.M.
AU - Curiel, David T.
AU - Scheper, Rik J.
AU - de Gruijl, Tanja D.
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Adenovirus
KW - Administration route
KW - Melanoma
UR - http://www.scopus.com/inward/record.url?scp=79951813688&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2011.01.022
DO - 10.1016/j.vaccine.2011.01.022
M3 - Article
C2 - 21272606
AN - SCOPUS:79951813688
SN - 0264-410X
VL - 29
SP - 2313
EP - 2321
JO - Vaccine
JF - Vaccine
IS - 12
ER -