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Human antibodies in cancer and autoimmune disease

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Abstract

In recent years, a number of novel human autoantigens and tumorassociated antigens have been identified using patient sera. Several of these antigens have been used as diagnostic markers, but defining their role in disease pathogenesis has been hampered by the lack of cloned human antibodies and antigens. Focusing on the solid cancers of the breast and colon and on autoimmune hematologic diseases, we are studying the role of human antibodies in disease pathogenesis. We have generated several, human monoclonal autoimmune and cancer-associated antibodies, using antibody phage display technology, and have identified, cloned, and expressed their corresponding (novel) antigens. Using the monoclonal human antibodies as probes, we are elucidating the processes that lead to the generation of these antibodies and their possible pathogenic or protective effect. These studies may lead to the development of reagents for diagnosis and therapeutic intervention of these important diseases.

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References

  1. Mach JP, Folli S, Pelegrin A., Magineres G, Calmes JM, Brainchotte D, Buchegger F, Hardman N, Heusser CH, Givel JC, Chapuis G, Chatelain A, van den Bergh H: Frontiers of Immunology and Cancer Immunology. New York, William Coley Symposium. The Cancer Research Institute 1993.

  2. Hakomori, S, Wang SM, Young WW Jr. Isoan tigenic expression of Forssman glycolipid in human gastric and colonic mucosa: its possible identity with “A-like antigen” in human cancer. Proc Natl Acad Sci USA 1977;74:3023–3027.

    Article  PubMed  CAS  Google Scholar 

  3. Real FX, Mattes MJ, Houghton AN, Ottgen HF, Lloyd KO, Old LJ: Class I (unique) tumorantigens of human melanoma. Identification of a 90,000 da Iton cell surface glycoprote in by autologues antibody. J Exp Med 1984;160:1219–1233.

    Article  PubMed  CAS  Google Scholar 

  4. Livingston PO, Wong GY, Adluri S, et al.: Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside. J Clin Oncol 1994;12: 1036–1044.

    PubMed  CAS  Google Scholar 

  5. Disis ML, Pupa SM, Gralow JR, Dittadi R, Menard S, Cheever MA: High-titer HER-2/neu protein-specific antibody can be detected in patients with early-stage breast cancer. J Clin Oncol 1997;15: 3363–3367.

    PubMed  CAS  Google Scholar 

  6. Kotera Y, Fontenol JD, Recher G, Metzgar RS, Finn OJ: Humoral immunity against a tandem repeal epitope of human mucin MUC-1 insera from breast, pancreatic, and colon cancer patients. Carscer Res 1994;54:2856–2860.

    CAS  Google Scholar 

  7. Cheever MA, Disis ML, Bernhard H, Gralow JR, Hand SL, Huseby ES, Qin HL, Takahashi M, Chen W: Immunity to oncogenic proteins. Immunol Rev 1995;145: 33–59.

    Article  PubMed  CAS  Google Scholar 

  8. Houbiers JG, van der Burg SH, van de Watering LM, Tollenaar RA, Brand A, van de Velde CJ, Melief CJ: Antibodies against p53 are associated with poor prognosis of colorectal cancer. Br J Cancer 1995;72:637–641.

    PubMed  CAS  Google Scholar 

  9. Schlichtholz B, Legros Y, Gillet D, Gaillard C, Marty M, Lane D, Calvo F, Soussi T: The immune response to p53 in breast cancer patients is directed a gairstimmun-odominant epitopes unrelated to the mutational hot spot. Cancer Res 1992;52:6380–6384.

    PubMed  CAS  Google Scholar 

  10. Balch CM, Riley LB, Bae YJ, Sameron MA, Platsoucas CD, Von Eschenbach A: Patterns of human tumor infiltrating lymphocytes in 120 human cancers. Arch Surg 1990;125:200–225.

    PubMed  CAS  Google Scholar 

  11. Petersen L, Zedeler K, Holck S, Schiodt T, Mouridsen HT: Medullary carcinoma of the breast, proposal for a new simplified histopathological definition. Br J Cancer 1991;63:591–595.

    Google Scholar 

  12. Petersen L, Zedeler K, Holck S, Schiodt T, Mouridsen HT: Meduliary carcinoma of the breast. Prevalence and prognostic importance of classical risk factors in breast cancer. Eur J Cancer 1995;312A:2289–2295.

    Article  Google Scholar 

  13. Mathoulin M-P, Xerri L, Jacquemier I, Adelaide J, Pare P, Hassoun J: Un restricted T-cell receptor V-region gene repertoire in tumor-infiltrating lymphocytes from human breast carcinomas. Cancer 1993;72:506–510.

    Article  PubMed  CAS  Google Scholar 

  14. Fuchs CS, Mayer RJ: Adjuvant chemotherapy for colon and rectal cancer. Semin Oncol 1995; 22:472–487.

    PubMed  CAS  Google Scholar 

  15. Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Goodman PJ, Underleider JS, Emaerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA: Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. NEJM 1990;322: 352–358.

    PubMed  CAS  Google Scholar 

  16. Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Goodman PJ, Underleider JS, Emaerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA: Fluorouracil plus leveamisole as effective adjuvant therapy after resection of state II colon carcinoma: A final report. Ann Intern Med 1995;122:321–326.

    PubMed  CAS  Google Scholar 

  17. Francini G, Petrioli R, Lorenzini L, et al.: Folinic acid and 5-fluoroura cilasadjuvan tchemo therapy in colon cancer. Gastroenterology 1994;106:899–906.

    PubMed  CAS  Google Scholar 

  18. Krook JE, Moertel CG, Gunderson LL, et al.: Effective surgical adjuvant therapy for high-risk rectal carcinomas. NEJM 1991; 324:709–715.

    PubMed  CAS  Google Scholar 

  19. O'connell MJ, Martenso JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, Mayer RJ, gunderson LL, Rich TA: Improving adjuvant therapy for rectal cancer by combining protracted-infusion flourouracil with radiation therapy after curative surgery. NEJM 1994;331:502–507.

    Article  PubMed  Google Scholar 

  20. Borup-Christensen P, Ern K, Jensenius JC, Nielsen B: Human hybridoma producing monoclonal antibodies against colorectal cancer-associated antigens. APMIS 1990;98:674–684.

    Article  PubMed  CAS  Google Scholar 

  21. Erb K, Borup-Christensen P, Ditzel H, Chemnitz J, Haas H, Jensenius JC: Characterization of a human-human hybridoma antibody, C-OUI, directed against a colon tumor-associated antigen Hybridoma 1992;11:121–134.

    Article  PubMed  CAS  Google Scholar 

  22. Ditzel HJ: Human monoclonal antibodies: a took for cancer detection in vivo. APMIS Suppl 1999; 94:5–42.

    PubMed  CAS  Google Scholar 

  23. Ditzel HJ, Rasmussen JW, Erb K, Borup-Christensen P, Jensenius JC: Biodistribution and tumor localization of 125I-labelled human IgM monoclonal antibody COU-I in nude mice bearing human tumor grafts. Antibody Immunoconj Radiopharm 1991;4: 507–515.

    CAS  Google Scholar 

  24. Ditzel HJ, Rasmussen JW, Erb K, Jensenius JC: Tumor localization and pharmacokinetics of 125I-labelled human IgM monoclonal antibody (COU-1) and its monomeric and half-monomeric fragments analyzed in humantumor-grafted nude mice. Eur J Nucl Med 1992;19:409–417.

    Article  PubMed  CAS  Google Scholar 

  25. Ditzel HJ, Rasmussen JW, Erb K, Borup-Christersen P, Titlestad I, Lassen E, Fenger C, Kronborg O, Jensenius JC: Tumor detection with 1311-labeled human monoclonal antibody COU-I in patients with suspected colorectal carcinoma. Cancer Res 1993;53: 5920–5928.

    PubMed  CAS  Google Scholar 

  26. Ditzel HJ, Rasmussen JW, Borup-Christersen P, Erb K, Jensenius JC, Phil D: Immunoscintigraphy of coloncancers with the human monocloral antibody COU-I. Cancer 1994;73:858–863.

    Article  PubMed  CAS  Google Scholar 

  27. Ditzel HJ, Garrigues U, Andersen CB, Larsen MK, Garrigues HJ. Svejgaard A, Hellstrom I, Hellstrom KE, Jersenius JC: Modified cytokeratins expressed on the surface of carcinoma cells undergo endocytosis upon binding of human monoclonal antibody and its recombinant fab fragment. Proc Natl Acad Sci USA 1997;94: 8110–8115.

    Article  PubMed  CAS  Google Scholar 

  28. Ditzel HJ: A utoimmune neutropenia; in Bona AN Theofilopolos An (eds): Mole cular Pathology of Autoimmunity. Gordon and Breach, Science Publisher, Langhorne, PA. in press.

  29. Goldberg J, Pinals RS: Felty'ssyndrome. Semin Arthritis Rheum 1980;10:52–65.

    Article  PubMed  CAS  Google Scholar 

  30. Shastri KA, Logue GL: Autoimmune neutropenia. Blood 1993:81: 1984–1995.

    PubMed  CAS  Google Scholar 

  31. Bux J, Mueller-Eckhardt C: Autoimmune neutropenia. Semin Hematol 1992;29:45–53.

    PubMed  CAS  Google Scholar 

  32. Sahin U, Tureci O, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I, Pfreundschuh M: Human Neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci USA 1995;92:11,810–11,813.

    CAS  Google Scholar 

  33. Old LJ, Chen YT: New paths in human carcerserology. J Exp Med 1998;187:1163–1167.

    Article  PubMed  CAS  Google Scholar 

  34. Folgori A, Tafi R, Meola A, Felici F, Galfre G, Cortese R, Monaci P, Nicosia A: A general strategy to identify mimotopes of pathological antigens using only random peptide libraries and human sera. EMBO J 1994;13:2236–2243.

    PubMed  CAS  Google Scholar 

  35. Ditzel HJ, Parren PWHI, Binley JM, Sodroski J, Moore JP, Barbas CF, Burton DR: Mapping the protein surface of human immunode-ficiency virus type 1 gp120 using human monoclonal antibodies from phage display libraries. J Mol Biol 1997;267:684–695.

    Article  PubMed  CAS  Google Scholar 

  36. Williamson RA, Burioni R, Sanna PP, Partridge LJ, Barbas CF, Burton RD: Human monoclonal antibodies against a plethora of viral pathogens from single combinatorial libraries. Proc Natl Acad Sci USA 1993;90:4141–4145.

    Article  PubMed  CAS  Google Scholar 

  37. De Kruif J, Terstappen L, Boel E, Logtenberg T: Rapid selection of cellsubpopulation-specific human monoclonal antibodies fromasynthetic phage antibody library. Proc Natl Acad Sci USA 1995;92: 3938–3942.

    Article  PubMed  Google Scholar 

  38. Marks JD, Ouwehand WH, Bye JM, Finnern R, Gorick BD, Voak V, Thorpe SJ, Hughes-Jones NC, Winter G: Human antibody fragments specific for human blood group antigens from phage display library. Bio/Technology 1993;11: 1145–1148.

    PubMed  CAS  Google Scholar 

  39. Ditzel HJ, Masaki Y, Nielsen H, Farnaes L, Burton DB: Cloning and expression of a novel human antibody/antigen pair associated with Felty's syndrome, submitted.

  40. Bierling P, Bettaieb A, Oksenhendler E: Human immuno deficiency virus-related immune thrombocytopenia. Semin Thromb Hemost 1995;21:68–75.

    Article  PubMed  CAS  Google Scholar 

  41. van der Lelie J, Lange JMA, Vos JJE, van Dalen CM, Danner SA, von dem Borne AEG: Autoimmunity against blood cells in human immunode ficiency-virus (HIV) infection. Br J Haematol 1987;67: 109–114.

    PubMed  Google Scholar 

  42. Walsh CM, Nardi MA, Karpatkin S: On the mechanism of thrombo-cytopenic purpura in sexually active homosexual men. NEJM 1984;311:635–639.

    PubMed  CAS  Google Scholar 

  43. Bettaieb A, Fromont P, Louache F, Oksenhendler E, Vainchenker W, Duedari N, Bierling P: Presence of cross-reactive antibody between human immunodeficiency virus (HIV) and platelet glycoproteins in HIV-related immune thrombo-cytopenic purpura. Blood 1992;80: 162–169.

    PubMed  CAS  Google Scholar 

  44. Karpatkin S, Nardi MA, Hymes KB: Sequestration of anti-platelet GPIIa antibody in rheumatoid factor immune complexes of human immunodeficiency virus 1 thrombocyto penic patients. PNAS 1995;92:2263–2267.

    Article  PubMed  CAS  Google Scholar 

  45. Klaassen RJL, van der Lelie J, Vlekke ABJ, Weigel HM, Eeftinch Schattenkerk JKM, Reiss P, von dem Borne AEGK: The serology and immunochemistry of HIV-induced platelet-bound immunoglobulin. Blut 1989;59:75–81.

    Article  PubMed  CAS  Google Scholar 

  46. Ditzel HJ, Burton DR: Antibody repertoire to self and the virus in HIV-1 infection probed by phage display libraries: in Chanock RM, Brown F, Ginsberg HS, Norrby E (eds): Vaccines 95, Plainview, NY. Cold Spring Harbor Laboratory Press, pp 19–26.

  47. Ditzel HJ, Itoh K, Burton DR: Determirants of polyreactivity in a large panel of recombinant human antibodies from HIV-1 infection. J Immunol 1996;157: 739–749.

    PubMed  CAS  Google Scholar 

  48. Ditzel HJ, Barbas SM, Barbas CF, Burton DR: The nature of the autoimmuneantibody repertoire in human immunodeficiency virus type 1 infection. Proc Natl Acad Sci USA 1994;91:3710–3714.

    Article  PubMed  CAS  Google Scholar 

  49. Nardi MA, Liu L-X, Karpatkin S: GP111a-(49–66) is a major pathophysio logically relevant antigenic determinant for anti-platelet GP111a of HIV-1-related immunologic thrombocytopenia. Proc Natl Acad Sci USA 1997;94: 7589–7594.

    Article  PubMed  CAS  Google Scholar 

  50. Borota R, Borota J, Belic A, Gebauer E, Stefanovic N, Dozic L: Effect of serum from thrombocy-topenic patients on platelet count in blood of mice. Med Pregl 1998;51:231–235.

    PubMed  CAS  Google Scholar 

  51. Burnet FM: Immunological Surveillance, Oxford, Pergamon Press, 1970; Thomas L; Discussion. In: Lawrence H.S., Ed., Cellular and Humoral Aspects of the Hypersensitive States, Hoeber-Harper, New York, 1959, pp. 529–532

    Google Scholar 

  52. NIH consensus conference. Adjuvant therapy for patients with colon

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Ditzel, H.J. Human antibodies in cancer and autoimmune disease. Immunol Res 21, 185–193 (2000). https://doi.org/10.1385/IR:21:2-3:185

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