PARTICULATE NATURALLY PROCESSED PEPTIDES PRIME A CYTOTOXIC RESPONSE AGAINST HUMAN-MELANOMA IN-VITRO

For an efficient antitumor cytotoxic response, tumor antigenic peptide s need to be presented by professional antigen-presenting cells in ass ociation with MHC class I molecules. We established in vitro short-ter m human CTL lines from healthy and melanoma-bearing subjects, using as antigen-presenting cells autologous adherent cells after phagocytosis of latex beads coated with melanoma peptides. Melanoma peptides were obtained by acid extraction of melanoma cells that matched with donor peripheral blood mononuclear cells, at least for one HLA-A allele. The cytotoxic activity of the lines was specific for the melanoma from wh ich peptides were obtained and for melanoma sharing HLA alleles. These results demonstrate that a complex mixture of naturally processed mel anoma peptides conjugated to a phagocytic substrate that targets them into the MHC class I pathway of adherent cells can prime a CTL respons e in healthy subjects in vitro, and that peptides from allogeneic tumo rs may be used to propagate CTL in melanoma patients. Our data support the feasibility of active and passive vaccination procedures with non living vaccines in cancer patients.