The generation and loading of dendritic cells (DC) ex-vivo for
tumor vaccination purposes is laborious and costly. Direct intradermal (i.d.) administration of
tumor-associated
antigens could be an attractive alternative approach, provided that efficient uptake and cross-presentation by appropriately activated skin DCs can be achieved. Here, we compare the efficiency of i.d. delivery of relatively small apoptotic
blebs (diameter ∼0.1-1 μm) derived from MART-1 transduced
acute myeloid leukemia (AML) HL60 cells, to that of larger apoptotic cell remnants (ACR; 2-10 μm) in a physiologically highly relevant human skin explant model. Injection of either fluorescently-labelled ACRs or
blebs alone did not affect the number or distribution of migrated DC subsets from skin biopsies after 48 hours, but resulted in a general up-regulation of the co-stimulatory molecules CD83 and CD86 on skin DCs that had ingested apoptotic material. We have previously shown that i.d. administration of
GM-CSF and
IL-4 resulted in preferential migration of a mature and highly T cell-stimulatory CD11hiCD1a+CD14- dermal DC subset. Here, we found that co-injection of
GM-CSF and
IL-4 together with either ACRs or
blebs resulted in uptake efficiencies within this dermal DC subset of 7.6% (±6.1%) and 19.1% (±15.9%), respectively, thus revealing a significantly higher uptake frequency of
blebs (P < 0.02). Intradermal delivery of
tumor-derived
blebs did not affect the T-cell priming and TH-skewing abilities of migratory skin DC. Nevertheless, in contrast to i.d. administration of ACR, the injection of
blebs lead to effective cross-presentation of MART-1 to specific CD8+ effector T cells. We conclude that apoptotic
bleb-based
vaccines delivered through the skin may offer an attractive, and broadly applicable,
cancer immunotherapy.