title: Immune responses to the 105AD7 human anti-idiotypic vaccine after intensive chemotherapy, for osteosarcoma.
abstract: 105AD7 is a human monoclonal antibody that mimics the complement regulatory protein, CD55, overexpressed by many solid tumours including osteosarcoma. This study was designed to assess the toxicity and efficacy of this vaccine in a young age group of patients within 1-6 months of myleosuppressive chemotherapy. Out of 28, 20 (71%, 95% CI 51-87%) patients showed a significant T-cell proliferation response in vitro to the 105AD7 protein but not to human IgG. Furthermore, 13 out of 22 (59%, 95% CI 36-79%) patients showed antigen-specific gammaIFN secretion (range 20-370 U/ml). Nine out of 28 (32%, 95% CI 16-52%) patients made weak antibody responses to CD55. This study showed that 105AD7 was well tolerated in younger patients with osteosarcoma. In addition, two patients with possible clinical responses were given compassionate permission to continue immunisation quarterly for 2 years. They both remain alive and disease free 5.8 and 6.5 years from original diagnosis of osteosarcoma and showed no adverse effects of repeated immunisation. In conclusion, the majority of patients showed measurable T helper responses when vaccination was commenced within a 6-month window of intensive chemotherapy with no clinically significant toxicity. Future clinical trials incorporating immune stimulation strategies should include early introduction of vaccines during the highest risk period for relapse.
authors.affiliation: Royal Marsden Hospital and Institute of Cancer Research, Downs Road, Sutton, Surrey SM2 5PT, UK.
authors.forename: K
authors.initials: K
authors.lastname: Pritchard-Jones
authors.forename: I
authors.initials: I
authors.lastname: Spendlove
authors.forename: C
authors.initials: C
authors.lastname: Wilton
authors.forename: J
authors.initials: J
authors.lastname: Whelan
authors.forename: S
authors.initials: S
authors.lastname: Weeden
authors.forename: I
authors.initials: I
authors.lastname: Lewis
authors.forename: J
authors.initials: J
authors.lastname: Hale
authors.forename: C
authors.initials: C
authors.lastname: Douglas
authors.forename: C
authors.initials: C
authors.lastname: Pagonis
authors.forename: B
authors.initials: B
authors.lastname: Campbell
authors.forename: P
authors.initials: P
authors.lastname: Alvarez
authors.forename: G
authors.initials: G
authors.lastname: Halbert
authors.forename: L G
authors.initials: LG
authors.lastname: Durrant
mesh_terms: D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018958:CD55 Antigens / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000187:drug effects / Q000276:immunology; D012516:Osteosarcoma / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: C405618:105AD7 antibody; D000888:Antibodies, Anti-Idiotypic; D018958:CD55 Antigens; D019496:Cancer Vaccines; D007371:Interferon-gamma