title: 105Ad7 cancer vaccine stimulates anti-tumour helper and cytotoxic T-cell responses in colorectal cancer patients but repeated immunisations are required to maintain these responses.
abstract: 105AD7 is a human anti-idiotypic antibody that recognises the binding site of the anti-tumour antibody 791T/36 and can thereby mimic the CD55 antigen. The molecular basis of 105AD7 mimicry has been identified with 3 CDR regions of 105AD7 showing similarity to 3 regions of CD55. These regions have been analysed for potential T-cell epitopes, and sequences that are predicted to bind to HLA/A1, 3,24 and to HLA/DR1,3,7 have been identified within the CDRH3 region of 105AD7. These epitopes should be stimulating CD8 and CD4 responses, respectively. This prediction was tested on 12 colorectal cancer patients receiving 105AD7 therapy. There was good concordance in 10 of 11 patients between accumulation of CD8RO cells or tumour killing and expression of HLA/A1,3,24. The only patient who failed to respond had a non-permissive class II haplotype and failed to show a helper response. Again 10 of 11 patients showing accumulation of CD4RO cells, in vitro blastogenesis responses, enhanced IL-2 or enhanced NK activity expressed one or more of the HLA/DR1,3,7 haplotypes. Although there was a consistent accumulation of CD45RO cells following 14 of 18 immunisations, only one patient showed a sustained memory response. Our results suggest that 105AD7 can stimulate CD4 and CD8 responses in patients with the appropriate haplotype. However, it may be necessary to continue to immunise, since few patients produce a sustained memory response.
authors.affiliation: CRC Department of Clinical Oncology, University of Nottingham, Nottingham, UK. lindy.durrant@nott.ac.uk
authors.forename: L G
authors.initials: LG
authors.lastname: Durrant
authors.forename: D J
authors.initials: DJ
authors.lastname: Buckley
authors.forename: R A
authors.initials: RA
authors.lastname: Robins
authors.forename: I
authors.initials: I
authors.lastname: Spendlove
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018958:CD55 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000628:therapy; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000187:drug effects; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D018958:CD55 Antigens; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D017493:Leukocyte Common Antigens