CELL-FREE TUMOR-ANTIGEN PEPTIDE-BASED CANCER VACCINES

The central role that tumor antigen-derived peptides play in induction of antitumor immunity makes them ideal candidates for peptide-based c ancer vaccines, We have demonstrated that ''transloading'' is an effic ient strategy for importing short peptide ligands into antigen-present ing cells in vitro, Postulating that the transloading procedure might effect peptide uptake by antigen-presenting cells in vivo as well, we tested this approach for the generation of peptide-based cancer vaccin es, In the P815 mastocytoma system, we vaccinated mice by s.c. injecti on of a single, known natural peptide derived from JAK-1 kinase, Where as vaccination with peptide alone or mixed with incomplete Freund's ad juvant was ineffective, application of the peptide in conjunction with the polycation poly-L-lysine protected a significant number of animal s against tumor challenge. Dependent upon the type of poly-L-lysine ap plied, protection against tumor take was comparable to that achieved w ith irradiated whole-cell vaccines, genetically modified to secrete gr anulocyte-macrophage colony-stimulating factor. In the murine melanoma M-3, a combination of four putative tumor antigen-derived peptides wa s tested as a cancer vaccine, Administered in combination with polycat ions, these peptides evoked potent antitumor immunity that could not b e obtained with the peptides alone or peptides emulsified in incomplet e Freund's adjuvant. However, peptide-polycation vaccines applied to t he M-3 model were not as efficient as cellular control vaccines, consi sting of irradiated interleukin 2 or granulocyte-macrophage colony-sti mulating factor-secreting turner cells.