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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 May 23;92(11):4773–4777. doi: 10.1073/pnas.92.11.4773

Human anti-idiotypic antibodies induced a humoral and cellular immune response against a colorectal carcinoma-associated antigen in patients.

J Fagerberg 1, M Steinitz 1, H Wigzell 1, P Askelöf 1, H Mellstedt 1
PMCID: PMC41789  PMID: 7539133

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.

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Selected References

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  1. Askelöf P., Rodmalm K., Wrangsell G., Larsson U., Svenson S. B., Cowell J. L., Undén A., Bartfai T. Protective immunogenicity of two synthetic peptides selected from the amino acid sequence of Bordetella pertussis toxin subunit S1. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1347–1351. doi: 10.1073/pnas.87.4.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bergenbrant S., Osterborg A., Holm G., Mellstedt H., Lefvert A. K. Anti-idiotypic antibodies in patients with monoclonal gammopathies: relation to the tumour load. Br J Haematol. 1991 May;78(1):66–70. doi: 10.1111/j.1365-2141.1991.tb04384.x. [DOI] [PubMed] [Google Scholar]
  3. Brown S. L., Miller R. A., Horning S. J., Czerwinski D., Hart S. M., McElderry R., Basham T., Warnke R. A., Merigan T. C., Levy R. Treatment of B-cell lymphomas with anti-idiotype antibodies alone and in combination with alpha interferon. Blood. 1989 Feb 15;73(3):651–661. [PubMed] [Google Scholar]
  4. Denton G. W., Durrant L. G., Hardcastle J. D., Austin E. B., Sewell H. F., Robins R. A. Clinical outcome of colorectal cancer patients treated with human monoclonal anti-idiotypic antibody. Int J Cancer. 1994 Apr 1;57(1):10–14. doi: 10.1002/ijc.2910570103. [DOI] [PubMed] [Google Scholar]
  5. Dolin R., Graham B. S., Greenberg S. B., Tacket C. O., Belshe R. B., Midthun K., Clements M. L., Gorse G. J., Horgan B. W., Atmar R. L. The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant gp160 candidate vaccine in humans. NIAID AIDS Vaccine Clinical Trials Network. Ann Intern Med. 1991 Jan 15;114(2):119–127. doi: 10.7326/0003-4819-114-2-119. [DOI] [PubMed] [Google Scholar]
  6. Durrant L. G., Buckley T. J., Denton G. W., Hardcastle J. D., Sewell H. F., Robins R. A. Enhanced cell-mediated tumor killing in patients immunized with human monoclonal antiidiotypic antibody 105AD7. Cancer Res. 1994 Sep 15;54(18):4837–4840. [PubMed] [Google Scholar]
  7. Fagerberg J., Frödin J. E., Ragnhammar P., Steinitz M., Wigzell H., Mellstedt H. Induction of an immune network cascade in cancer patients treated with monoclonal antibodies (ab1). II. Is induction of anti-idiotype reactive T cells (T3) of importance for tumor response to mAb therapy? Cancer Immunol Immunother. 1994 Mar;38(3):149–159. doi: 10.1007/BF01525635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fields G. B., Noble R. L. Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. Int J Pept Protein Res. 1990 Mar;35(3):161–214. doi: 10.1111/j.1399-3011.1990.tb00939.x. [DOI] [PubMed] [Google Scholar]
  9. Frödin J. E., Faxas M. E., Hagström B., Lefvert A. K., Masucci G., Nilsson B., Steinitz M., Unger P., Mellstedt H. Induction of anti-idiotypic (ab2) and anti-anti-idiotypic (ab3) antibodies in patients treated with the mouse monoclonal antibody 17-1A (ab1). Relation to the clinical outcome--an important antitumoral effector function? Hybridoma. 1991 Aug;10(4):421–431. doi: 10.1089/hyb.1991.10.421. [DOI] [PubMed] [Google Scholar]
  10. Herlyn D., Wettendorff M., Schmoll E., Iliopoulos D., Schedel I., Dreikhausen U., Raab R., Ross A. H., Jaksche H., Scriba M. Anti-idiotype immunization of cancer patients: modulation of the immune response. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8055–8059. doi: 10.1073/pnas.84.22.8055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Herlyn M., Steplewski Z., Herlyn D., Koprowski H. Colorectal carcinoma-specific antigen: detection by means of monoclonal antibodies. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1438–1442. doi: 10.1073/pnas.76.3.1438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Koprowski H., Herlyn D., Lubeck M., DeFreitas E., Sears H. F. Human anti-idiotype antibodies in cancer patients: Is the modulation of the immune response beneficial for the patient? Proc Natl Acad Sci U S A. 1984 Jan;81(1):216–219. doi: 10.1073/pnas.81.1.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mellstedt H., Frödin J. E., Biberfeld P., Fagerberg J., Giscombe R., Hernandez A., Masucci G., Li S. L., Steinitz M. Patients treated with a monoclonal antibody (ab1) to the colorectal carcinoma antigen 17-1A develop a cellular response (DTH) to the "internal image of the antigen" (ab2). Int J Cancer. 1991 May 30;48(3):344–349. doi: 10.1002/ijc.2910480306. [DOI] [PubMed] [Google Scholar]
  14. Mellstedt H., Frödin J. E., Masucci G., Ragnhammar P., Fagerberg J., Hjelm A. L., Shetye J., Wersäll P., Osterborg A. The therapeutic use of monoclonal antibodies in colorectal carcinoma. Semin Oncol. 1991 Oct;18(5):462–477. [PubMed] [Google Scholar]
  15. Mittelman A., Chen Z. J., Yang H., Wong G. Y., Ferrone S. Human high molecular weight melanoma-associated antigen (HMW-MAA) mimicry by mouse anti-idiotypic monoclonal antibody MK2-23: induction of humoral anti-HMW-MAA immunity and prolongation of survival in patients with stage IV melanoma. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):466–470. doi: 10.1073/pnas.89.2.466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ohlin M., Sundqvist V. A., Gilljam G., Rudén U., Gombert F. O., Wahren B., Borrebaeck C. A. Characterization of human monoclonal antibodies directed against the pp65-kD matrix antigen of human cytomegalovirus. Clin Exp Immunol. 1991 Jun;84(3):508–514. [PMC free article] [PubMed] [Google Scholar]
  17. Pride M. W., Thakur A., Thanavala Y. Mimicry of the a determinant of hepatitis B surface antigen by an antiidiotypic antibody. I. Evaluation in hepatitis B surface antigen responder and nonresponder strains. J Exp Med. 1993 Jan 1;177(1):127–134. doi: 10.1084/jem.177.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Riethmüller G., Schneider-Gädicke E., Schlimok G., Schmiegel W., Raab R., Höffken K., Gruber R., Pichlmaier H., Hirche H., Pichlmayr R. Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma. German Cancer Aid 17-1A Study Group. Lancet. 1994 May 14;343(8907):1177–1183. doi: 10.1016/s0140-6736(94)92398-1. [DOI] [PubMed] [Google Scholar]
  19. Robins R. A., Denton G. W., Hardcastle J. D., Austin E. B., Baldwin R. W., Durrant L. G. Antitumor immune response and interleukin 2 production induced in colorectal cancer patients by immunization with human monoclonal anti-idiotypic antibody. Cancer Res. 1991 Oct 1;51(19):5425–5429. [PubMed] [Google Scholar]
  20. Steinitz M., Tamir S., Frödin J. E., Lefvert A. K., Mellstedt H. Human monoclonal anti-idiotypic antibodies. I. Establishment of immortalized cell lines from a tumor patient treated with mouse monoclonal antibodies. J Immunol. 1988 Nov 15;141(10):3516–3522. [PubMed] [Google Scholar]
  21. Strassburg C. P., Kasai Y., Seng B. A., Miniou P., Zaloudik J., Herlyn D., Koprowski H., Linnenbach A. J. Baculovirus recombinant expressing a secreted form of a transmembrane carcinoma-associated antigen. Cancer Res. 1992 Feb 15;52(4):815–821. [PubMed] [Google Scholar]

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