Generation of immunity to the HER-2/neu oncogenic protein in patients withbreast and ovarian cancer using a peptide-based vaccine

HER-2/neu is a "self" tumor antigen that is overexpressed in 15-30% of huma n adenocarinomas, Vaccine strategies directed against HER-2/neu and other s elf tumor antigens require development of methods to overcome immune tolera nce to self-proteins. In rats, rat neu peptide vaccines have been shown to be an effective way of circumventing tolerance to rat neu protein and gener ating rat neu-specific immunity. The present report validates that a simila r peptide-based vaccine formulation is effective for inducing T-cell immuni ty to HER-2/neu protein in humans with breast and ovarian cancer. The vacci ne formulation included groups of peptides derived from the HER-2/neu extra cellular domain (ECD) or intracellular domain (ICD) mixed with granulocyte macrophage colony stimulating factor as an adjuvant, These peptides were 15 -18 amino acids in length and designed to elicit a CP4 T helper-specific im mune response. Patients underwent intradermal immunization once a month for a total of two to six immunizations, To date, all of the patients immunize d with HER-2/neu peptides developed HER-2/neu peptide-specific T-cell respo nses. The majority of patients (six of eight) also developed HER-2/lieu pro tein-specific responses. Responses to HER-2/neu protein occurred with epito pe spreading. Immune T cells elicited by vaccination were shown to migrate outside the peripheral circulation by virtue of generating delayed type hyp ersensitivity responses distant from the vaccine site, which indicated the potential ability to traffic to the site of tumor. The use of peptide-based vaccines may be a simple, yet effective, vaccine strategy for immunizing h umans to oncogenic self-proteins.