Phase I clinical trial of a human idiotypic p53 vaccine in patients with advanced malignancy

Background: The purpose of this study was to induce immunity to p53 by using an idiotypic vaccine, composed of a pool of eight peptides derived from the complimentarily determining regions (CDRs) of human anti-p53 antibodies. Patients and methods: Subjects with advanced malignancy received up to four, monthly intradermal injections of pooled peptides (500 mug of each) admixed with granulocyte-macrophage colony-stimulating factor (GM-CSF; 100 mug). In addition, two sheep and two rabbits were also vaccinated with the pooled peptides. Results: Fourteen subjects were enrolled into the study and six of these completed the vaccination schedule. The vaccine was well tolerated by all subjects and no major adverse events were attributable to the vaccine. All subjects mounted in vivo delayed type hypersensitivity (DTH) responses to two or more of the individual vaccine peptides. Vaccine-induced antibodies specific for peptides 2, 5 or 8 were detected in four of six subjects, and two of these had vaccine-specific, cell-mediated responses. Increasing titers of p53-specific antibodies were found in one patient. No T-cell response to p53 was observed in any of the subjects. All animals developed humoral immunity to the peptides and one of the sheep developed rising serum titers of anti-p53 antibodies. Conclusions: Vaccination with human antibody CDR regions represents a novel method for inducing human antibodies, which may in turn serve as immunological mimics of p53.