title: Human anti-idiotypic antibodies induced a humoral and cellular immune response against a colorectal carcinoma-associated antigen in patients.
abstract: Induction of immunity against antigens expressed on tumor cells might prevent or delay recurrence of the disease. Six patients operated on for colorectal carcinoma were immunized with human monoclonal anti-idiotypic antibodies (h-Ab2) against the mouse 17-1A anti-colon carcinoma antibody, mimicking a nominal antigen (GA733-2). All patients developed a long-lasting T-cell immunity against the extracellular domain of GA733-2 (GA733-2E) (produced in a baculovirus system) and h-Ab2. This was shown in vitro by specific cell proliferation (DNA-synthesis) assay as well as by interleukin 2 and interferon gamma production and in vivo by the delayed-type hypersensitivity reaction. Five patients mounted a specific humoral response (IgG) against the tumor antigen GA733-2E (ELISA) and tumor cells expressing GA733-2. Epitope mapping using 23 overlapping peptides of GA733-2E revealed that the B-cell epitope was localized close to the N terminus of GA733-2. Binding of the antibodies to the tumor antigen and to one 18-aa peptide was inhibited by h-Ab2, indicating that the antibodies were able to bind to the antigen as well as to h-Ab2. The results suggest that our h-Ab2 might be able to induce an anti-tumor immunity which may control the growth of tumor cells in vivo.
authors.affiliation: Department of Oncology (Radiumhemmet), Karolinska Hospital, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Fagerberg
authors.forename: M
authors.initials: M
authors.lastname: Steinitz
authors.forename: H
authors.initials: H
authors.lastname: Wigzell
authors.forename: P
authors.initials: P
authors.lastname: Askelöf
authors.forename: H
authors.initials: H
authors.lastname: Mellstedt
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology*; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D000071858:Epithelial Cell Adhesion Molecule; D000939:Epitopes / Q000032:analysis; D006801:Humans; D007111:Immunity, Cellular; D007115:Immunization Schedule; D007167:Immunotherapy; D007700:Kinetics; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D008875:Middle Aged; D009367:Neoplasm Staging; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D018411:Spodoptera; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D000939:Epitopes; D011994:Recombinant Proteins