Development and Characterization of Human Monoclonal Antibodies and Their Application in the Radioimmunodetection of Colon Carcinoma

  • Richard P. McCabe
  • Leona C. Peters
  • Martin V. Haspel
  • Nicholas Pomato
  • Jorge A. Carrasquillo
Part of the NATO ASI Series book series (NSSA, volume 152)


Significant progress has been made in the application of monoclonal antibody technology to clinical diagnosis of cancer and to management of the disease. Antibodies labeled with radioactive isotopes have been demonstrated to localize in tumors of the gastrointestinal tract (1–6), ovary (6), breast (6,7), and skin (8) and promise to be very helpful in identifying metastases in patients with these tumors. However, there remain several problems to be resolved before radiolabeled antibody detection of tumor foci will be applied as an accepted and routine diagnostic/prognostic procedure. Problems include antibody cross-reactivity with normal tissues (5,6,9,10), low level penetration of antibody into tumor tissue (5,9,10), and inhibitory effects of specific circulating antigen (11). Current research is focused on selecting antibodies with the most desirable characteristics for tumor detection, improving chemistries to allow use of more appropriate radionuclides, and defining the effective clinical applications with regard to the tumor types, tumor sites and available diagnostic equipment and procedures.


Colon Tumor Human Monoclonal Antibody Bacillus Calmette Guerin Normal Colon Tumor Detection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    D. M. Goldenberg, F. H. Deland, and E. Kim, Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning, N. Engl. J. Med. 298:1384 (1978).PubMedCrossRefGoogle Scholar
  2. 2.
    C. Berche, J. P. Mach, J. D. Lumbroso, C. Langlais, F. Aubry, F. Buchegger, S. Carrel, P. Rougier, C. Parmentier, and M. Tubiana, Tomoscintigraphy for detecting gastrointestinal and medullary thyroid cancers: First clinical results using radiolabeled monoclonal antibodies against carcinoembryonic antigen, Br. Med. J. 285:1447 (1982).CrossRefGoogle Scholar
  3. 3.
    J. F. Chatal, J. C. Saccavini, P. Fumoleau, J. Y. Douillard, C. Curtet, M. Kremer, B. LeMevel, and H. Koprowski, Immunoscintigraphy of colon carcinoma, J. Nucl. Med. 25:307 (1984).PubMedGoogle Scholar
  4. 4.
    N. C. Armitage, A. C. Perkins, M. V. Pimm, P. A. Farrands, R. W. Baldwin, and J. D. Hardcastle, The localization of an anti-tumor monoclonal antibody (791T/36) in gastrointestinal tumors, Br. J. Surgery 74:407 (1984).CrossRefGoogle Scholar
  5. 5.
    J. P. Mach, J. F. Chatal, J. D. Lumbroso, F. Buchegger, M. Forni, J. Ritschard, C. Berche, J. Y. Douillard, S. Carrel, M. Herlyn, Z. Steplewski, and H. Koprowski, Tumor localization in patients by radiolabeled monoclonal antibodies against colon carcinoma, Cancer Res. 43:5593 (1983).PubMedGoogle Scholar
  6. 6.
    A. A. Epenetos, K. E. Britton, J. Mather, J. Shepherd, M. Granowska, J. Taylor-Papadimitriou, C. C. Nimmon, H. Durbin, L. R. Hawkins, and J.S. Malpas, Targeting of iodine-123-labeled tumor-associated monoclonal antibodies to ovarian, breast, and gastrointestinal tumors, Lancet 2:999 (1982).PubMedCrossRefGoogle Scholar
  7. 7.
    R. M. Rainsbury, J. H. Westwood, R. C. Coombes, A. M. Neville, R. J. Ott, T. S. Kalivai, V. R. McCready, and J. C. Gazet, Location of metastatic breast carcinoma by a monoclonal antibody chelate labeled with indium-111, Lancet 2:934 (1983).PubMedCrossRefGoogle Scholar
  8. 8.
    J. A. Carrasquillo, K. A. Krohn, P. Beaumier, R. W. McGuffin, J. P. Brown, K. Brown, K. E. Hellstrom, I. Hellstrom, and S. M. Larson, Diagnosis and therapy for solid tumors with radiolabeled antibodies and immune fragments, Cancer Treat. Rep. 68:317 (1984).PubMedGoogle Scholar
  9. 9.
    S. M. Larson, J. P. Brown, P. W. Wright, J. A. Carrasquillo, I. Hellstrom, and K. E. Hellstrom, Imaging of melanoma with I-131 labeled monoclonal antibodies, J. Nucl. Med. 24:123 (1983).PubMedGoogle Scholar
  10. 10.
    P. J. Moldofsky, J. Powe, C. B. Mulherne, U. Hammond, H. F. Sears, P.A. Gatenby, Z. Steplewski, and H. Koprowski, Metastatic colon carcinoma detected with radiolabeled F(ab′)2 monoclonal antibody fragments. Radiology 149:549 (1983).PubMedGoogle Scholar
  11. 11.
    P. L. Hagan, S. E. Halpern, A. Chen, L. Krishnan, J. Frincke, R. M. Bartholomew, G. S. David, and D. Carlo, In vivo kinetics of radiolabeled monoclonal anti-CEA antibodies in animal models, J. Nucl. Med. 26:1418 (1985).PubMedGoogle Scholar
  12. 12.
    R. K. Oldham, Monoclonal antibodies in cancer therapy, J. Clin. Oncol. 1:582 (1983).PubMedGoogle Scholar
  13. 13.
    R. Levy, and R. A. Miller, Tumor therapy with monoclonal antibodies, Fed. Proc. 42:2650 (1983).Google Scholar
  14. 14.
    H. V. Pimm, A. C. Perkins, N. C. Armitage, and R. W. Baldwin, The characteristics of blood borne radiolabels and the effect of antimouse IgG antibodies on localization of radiolabeled monoclonal antibody in cancer patients, J. Nucl. Med. 26:1011 (1985).PubMedGoogle Scholar
  15. 15.
    J. C. Reynolds, J. A. Carrasquillo, A. M. Keenan, M. E. Lora, P. Sugarbaker, P. Abrams, K. Foon, J. L. Mulshine, J. Roth, D. Colcher, J. Schlom, and S. M. Larson, Human anti-murine antibodies following immunoscintigraphy or therapy with radiolabelled monoclonal antibodies, J. Nucl. Med. 27:1022 (1986).Google Scholar
  16. 16.
    R. W. Schroff, K. A. Foon, S. M. Beatty, R. K. Oldham, and A. C. Morgan, Human anti-murine immunoglobulin responses in patients receiving monoclonal antibody therapy, Cancer Res. 45:869 (1985).Google Scholar
  17. 17.
    H. F. Sears, D. Herlyn, A. Steplewski, and H. Koprowski, Effects of monoclonal antibody immunotherapy on patients with gastrointestinal adenocarcinoma, J. Biol. Response Mod. 3:138 (1974).Google Scholar
  18. 18.
    D. L. Shawler, R. M. Bartholomew, L. M. Smith, and R. O. Dillman, Human immune response to multiple injections of murine monoclonal IgG, J. Immunol. 135:1530 (1985).PubMedGoogle Scholar
  19. 19.
    B. Ballou, J. M. Reiland, G. Levine, R. J. Taylor, W. C. Shen, H. J. Ryser, D. Solter, and T. R. Hakala, Tumor location and drug targeting using a monoclonal antibody (anti-SSEA-1) and antigen binding fragments, J. Surg. Oncol. 31:1 (1986).PubMedCrossRefGoogle Scholar
  20. 20.
    T. Maillet, A. C. Roche, F. Therain, and M. Mosigny, Time course localization of immunoglobulin M monoclonal antibody and its fragments in leukemic tumor-bearing mice, Cancer Immunol. Immunother. 19:177 (1985).PubMedCrossRefGoogle Scholar
  21. 21.
    S. L. Morrison, M. J. Johnson, L. A. Herzenbern, and Oi, V. T., Chimeric human antibody molecules: Mouse antigen-binding domains with human constant region domains, Proc. Natl. Acad. Sci. USA, 81:6851 (1984).PubMedCrossRefGoogle Scholar
  22. 22.
    L. K. Sun, P. Curtis, E. Rakowicz-Szulczynska, J. Ghrayeh, N. Chang, S. L. Morrison, and H. Koprowski, Chimeric antibody with human constant regions and mouse variable regions directed against carcinoma-associated antigen 17-1A, Proc. Natl. Acad. Sci. USA, 84:214 (1987).PubMedCrossRefGoogle Scholar
  23. 23.
    J. Schlom, D. Wunderlich, and U. A. Teramoto, Generation of human monoclonal antibodies reactive with human mammary carcinoma cells, Proc. Natl. Acad. Sci. USA, 77:6841 (1980).PubMedCrossRefGoogle Scholar
  24. 24.
    K. Sikora, and R. Wright, Human monoclonal antibodies to lung cancer antigens, Br. J. Cancer, 43:696 (1981).PubMedCrossRefGoogle Scholar
  25. 25.
    J. Sikora, T. Alderson, A. Nethersell, and H. Smedley, Tumor localization by human monoclonal antibodies, Med. Oncol. Tumour Pharmacother 2:77 (1985).Google Scholar
  26. 26.
    R. J. Cote, D. M. Morrissey, A. N. Houghton, E. J. Beattie, Jr., H. F. Oettgen, and L. J. Old, Generation of human monoclonal antibodies reactive with cellular antigens, Proc. Natl. Acad. Sci. USA, 80:2026 (1983).PubMedCrossRefGoogle Scholar
  27. 27.
    A. Iman, M. M. Drushella, C. R. Taylor, and Z. Tokes, Generation and immunohistological characterization of human monoclonal antibodies to mammary carcinoma cells, Cancer Res. 45:263 (1985).Google Scholar
  28. 28.
    M. G. Hanna, Jr. and L. C. Peters, Immunotherapy of established micrometastases with a Bacillus Calmette Guerin tumor cell vaccine, Cancer Res. 38:204 (1978).PubMedGoogle Scholar
  29. 29.
    M. G. Hanna, Jr., J. S. Brandhorst, and L. C. Peters, Active specific immunotherapy of residual micrometastases: An evaluation of sources, doses and ratios of BCG with tumor cells, Cancer Immunol. Immunother. 7:165 (1979).CrossRefGoogle Scholar
  30. 30.
    H. C. Hoover, Jr., M. Surkyke, R. B. Dangel, L. C. Peters, and M. G. Hanna, Jr., Delayed cutaneous hypersensitivity to autologous tumor cells in colorectal cancer patients immunized with an autologous tumor cell-Bacillus Calmette Guerin vaccine, Cancer Res. 44:1671 (1984).PubMedGoogle Scholar
  31. 31.
    H. C. Hoover, Jr., M. G. Surdyke, R. B. Dangel, L. C. Peters, and M. G. Hanna, Jr., Prospectively randomized trial of adjuvant active specific immunotherapy for human colorectal cancer, Cancer 55:1236 (1985).PubMedCrossRefGoogle Scholar
  32. 32.
    L. C. Peters, J. S. Brandhorst, and M. G. Hanna, Jr., Preparation of immunotherapeutic autologous tumor cell vaccines from solid tumors. Cancer Res. 39:1353 (1979).PubMedGoogle Scholar
  33. 33.
    L. C. Peters, and M. G. Hanna, Jr., Active specific immunotherapy of established metastases: Effect of cryopreservation procedures on tumor cell immunogenicity in guinea pigs. J. Nat’l. Cancer Inst. 64:1521 (1980).Google Scholar
  34. 34.
    M. V. Haspel, R. P. McCabe, N. J. Pomato, J. V. Knowlton, L. C. Peters, H. C. Hoover, Jr., M. G. Hanna, Jr., Generation of tumor cell-reactive human monoclonal antibodies using peripheral blood lymphocytes from actively immunized colorectal carcinoma patients, Cancer Res. 45:3951 (1985).PubMedGoogle Scholar
  35. 35.
    H. F. Dvorak, N. S. Orenstein, A. C. Carvalho, W. H. Churchill, A. M. Dvorak, S. J. Galli, J. Feder, A. M. Bitzer, J. Rypysc, and P. Giorinco, Induction of a fibringel investment: An early event in line 10 hepatocarcinoma growth mediated by tumor secreted products, J. Nat’l. Cancer Inst. 122:166 (1979)Google Scholar
  36. 36.
    W. F. Barth, R. D. Wochner, T. Waldmann, and J. L. Fahey, Metabolism of human gamma macroglobulins, J. Clin. Invest. 6:1036 (1964).CrossRefGoogle Scholar
  37. 37.
    R. P. McCabe, L. C. Peters, M. V. Haspel, N. Pomato, J. A. Carrasquillo, M. G. Hanna, Jr., Human monoclonal antibodies to colorectal cancer: preclinical pharmacokinetic and tumor localization studies, Proc. Amer. Assoc. Cancer Res. (In Press).Google Scholar
  38. 38.
    R. P. McCabe, L. C. Peters, M. V. Haspel, N. Pomato, J. A. Carrasquillo, M. G. Hanna, Jr., Preclinical pharmacokinetic and tumor localization studies with human monoclonal antibodies to colorectal cancer, Cancer Res. (In press).Google Scholar
  39. 39.
    B. Ballou, J. Reiland, G. Levine, B. Knowles, and T. R. Hakala, Tumor location using F(ab′)2 from a monoclonal IgM antibody: pharmacokinetics, J. Nucl. Med., 26:283 (1985).PubMedGoogle Scholar
  40. 40.
    R. W. Baldwin, and M. V. Pimm, Anti-tumor monoclonal antibodies for radioimmunodetection of tumors and drug targeting, Cancer Metastasis Rev. 2:89 (1983).PubMedCrossRefGoogle Scholar
  41. 41.
    A. A. Epenetos, W. F. Bodmer and K. E. Britton, Radioimmunodetection of cancer, Eur. J. Cancer Clin. Oncol. 18:1221 (1982).PubMedCrossRefGoogle Scholar
  42. 42.
    D. Herlyn, J. Powe, A. Alavi, J. A. Mattis, M. Herlyn, C. Ernst, R. Vaum, and H. Koprowski, Radioimmunodetection of human tumor xenografts by monoclonal antibodies, Cancer Res. 43:2731 (1983).PubMedGoogle Scholar
  43. 43.
    B. Ballou, G. Levine, T. R. Hakala, and D. Solter, Tumor location detected with radioactively labeled monoclonal antibody and external scintigraphy, Science 206:844 (1979).PubMedCrossRefGoogle Scholar
  44. 44.
    A. Hedin, B. Wahren, and S. Hammarstrom, Tumor localization of CEA containing human tumors in nude mice by means of monoclonal anti CEA antibodies, Int. J. Cancer 30:547 (1982).PubMedCrossRefGoogle Scholar
  45. 45.
    T. Nakamura, H. Sakahara, S. Hosoi, T. Yamamuro, S. Higashi, H. Mikawo, K. Endo, and S. Tomaya, In vivo radiolocalization of anti osteogenic sarcoma xenografts, Cancer Res. 44:2078 (1984).PubMedGoogle Scholar
  46. 46.
    D. S. Reintgen, K. Shimizu, E. Coleman, W. Briner, J. Kitzmiller, G. Eisenbarth and H. F. Seigier, Immunodiagnosis of tumors in vivo using radiolabeled monoclonal antibody A2B5, J. Surg. Oncol. 23:205 (1983).PubMedCrossRefGoogle Scholar
  47. 47.
    D. Hyams, J. C. Reynolds, J. A. Carrasquillo, P. Perentesis. S. M. Larson, M. Morin, D. Simpson, J. Schlom, and D. Colcher, The effect of circulating anti-murine antibody on the pharmacokinetics and biodistribution of injected radiolabeled monoclonal antibody, J. Nucl. Med. 27:922 (1986).Google Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Richard P. McCabe
    • 1
  • Leona C. Peters
    • 1
  • Martin V. Haspel
    • 1
  • Nicholas Pomato
    • 1
  • Jorge A. Carrasquillo
    • 1
    • 2
  1. 1.Bionetics Research, Inc.RockvilleUSA
  2. 2.Department of Nuclear MedicineNational Institutes of HealthBethesdaUSA

Personalised recommendations