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* Division of Immunology, Allergy, and Infectious Diseases, Department of Dermatology, University of Vienna Medical School, and
Intercell AG, Vienna, Austria; and
Department of Dermatology, University School of Medicine, Essen, Germany
The s.c injection of tumor Ag-derived, MHC class I-binding peptides
together with cationic poly-amino acids (e.g.,
poly-L-arginine; pR) has been shown to protect animals
against a challenge with tumor cells expressing the respective
peptide(s). Given our only restricted knowledge about immunogenic
tumor-associated peptides, we sought to determine whether this pR-based
vaccination protocol would also induce protective cancer immunity if
large proteins were used instead of peptide epitopes. We found that the
intracutaneous administration of the model Ag 
-galactosidase
(-gal) together with pR (referred to as pR-based protein vaccine;
pR-PV) was significantly more potent in protecting mice against the
growth of -gal-expressing RENCA cells than the protein alone.
Coadministration of pR enhanced both the -gal-induced specific
humoral and CD8 response. The protective effect required
CD8+, but neither CD4+ T lymphocytes nor
-gal-specific Abs. -Gal priming of protective CD8+ T
lymphocytes was found to be CD4+ T cell-independent, to
take place within the draining lymph nodes, and to be accomplished by
day 5 after vaccination. Ablation of the injection sites as early as
1.5 h after pR-PV administration still led to protection in a
large proportion of the animals, indicating that certain protein Ags
administered intradermally in the context of polycations are quickly
transported to the draining nodes, where they induce molecular and
cellular events resulting in the helper-independent priming and
expansion of Tc1 cells. However, optimal protection required the
prolonged presence of the injection site, suggesting that pR-PV
injection facilitates the formation of a cutaneous depot of Ag-charged
cells capable of migration and T cell
activation.
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