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Diagnostic and therapeutic applications of monoclonal antibodies in colorectal cancer


PURPOSE: The study contained herein was undertaken to review and summarize the current literature on diagnostic and therapeutic applications of monoclonal antibodies in colorectal cancer. RESULTS: Limitations of traditional imaging techniques have encouraged development of targeted imaging strategies using radiolabeled monoclonal antibodies. Diagnostic immunoscintigraphy can detect lesions not identified by conventional imaging modalities, although it has not proven useful in the management of primary colorectal cancers and in hepatic metastases. Immunoscintigraphy shows promise in cases of local recurrence and rising carcinoembryonic antigen values; however, the impact of immunoscintigraphy on clinical outcomes and cost-effectiveness remains unproven. Radioimmunoguided surgery has been advocated as a method of more accurately detecting tumor extension and accomplishing radical resection. The technique remains controversial, and its use is not widespread. With respect to therapeutic applications, immunotherapy has most often been investigated in the setting of advanced stage disease. Results in this setting have been poor. In contrast, adjuvant immunotherapy after resection of Dukes C carcinoma has achieved convincing results, with improvements in survival comparable with that of adjuvant chemotherapy. Adjuvant trials are now under way to examine the effectiveness of monoclonal antibodies in the postoperative treatment of early-stage (II) tumors and the combination of monoclonal antibodies and chemotherapy in advanced-stage (III) tumors. Bispecific antibodies, or immunoconjugates with cytokines or toxins, represent additional areas of interest and future investigations. CONCLUSIONS: At present, immunoscintigraphy is not sufficient to determine, by itself, resectability of colorectal tumor and has limited usefulness in select cases of recurrent cancer and possibly in cases of rising carcinoembryonic antigen values. Immunotherapy with monoclonal antibodies as a postoperative adjuvant treatment shows promise and is currently being investigated in national trials.

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  1. 1.

    Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975;256:495–7.

  2. 2.

    Schroff RW, Foon KA, Beatty SM, Oldham RK, Morgan AC Jr. Human anti-murine immunoglobulin responses in patients receiving monoclonal antibody therapy. Cancer Res 1985;45:879–85.

  3. 3.

    Haseman MK, Brown DW, Keeling CA, Reed NL. Radioimmunodetection of occult carcinoembryonic antigen-producing cancer. J Nucl Med 1992;33:1750–6.

  4. 4.

    Collier BD, Abdel-Nabi H, Doerr RJ,et al. Immunoscintigraphy performed with In-111-labeled CYT-103 in the management of colorectal cancer: comparison with CT. Radiology 1992;185:179–86.

  5. 5.

    Doerr RJ, Abdel-Nabi H, Krag D, Mitchell E. Radiolabeled antibody imaging in the management of colorectal cancer: results of a multicenter clinical study. Ann Surg 1991;214:118–24.

  6. 6.

    Steinstrasser A, Oberhausen E. Anti-CEA labelling kit BW 431/26: results of the European multicenter trial. Nuklearmedizin 1995;34:232–42.

  7. 7.

    Corman ML, Galandiuk S, Block GE,et al. Immunoscintigraphy with 111In-satumomab pendetide in patients with colorectal adenocarcinoma: performance and impact on clinical management. Dis Colon Rectum 1994;37:129–37.

  8. 8.

    Dillman RO, Shawler DL, McCallister TJ, Halpern SE. Human anti-mouse antibody response in cancer patients following single low-dose injections of radiolabeled murine monoclonal antibodies. Cancer Bioth 1994;9:17–28.

  9. 9.

    Lind P, Lechner P, Arian-Schad K,et al. Anticarcinoembryonic antigen immunoscintigraphy (technetium-99m-monoclonal antibody BW 431/26) and serum CEA levels in patients with suspected primary and recurrent colorectal carcinoma. J Nucl Med 1991;32:1319–25.

  10. 10.

    Abdel-Nabi HH, Doerr RJ, Chan HW,et al. Safety and role of repeated administrations of Indium-111-labeled anti-carcinoembryonic antigen monoclonal antibody ZCE 025 in the postoperative follow-up of colorectal carcinoma patients. J Nucl Med 1992;33:14–22.

  11. 11.

    Frodin JE, Lefvert AK, Mellstedt H. Pharmacokinetics of the mouse monoclonal antibody 17-1A in cancer patients receiving various treatment schedules. Cancer Res 1990;50:4866–71.

  12. 12.

    Colcher D, Milenic DE, Ferroni P,et al. In vivo fate of monoclonal antibody B72.3 in patients with colorectal cancer. J Nucl Med 1990;31:1133–42.

  13. 13.

    Ledermann JA, Begent RH, Massof C, Kelly AM, Adam T, Bagshawe KD. A phase-I study of repeated therapy with radiolabelled antibody to carcinoembryonic antigen using intermittent or continuous administration of cyclosporin A to suppress the immune response. Int J Cancer 1991;47:659–64.

  14. 14.

    Dhingra K, Fritsche H, Murray JL,et al. Phase I clinical and pharmacological study of suppression of human antimouse antibody response to monoclonal antibody L6 by deoxyspergualin. Cancer Res 1995;55:3060–7.

  15. 15.

    Morton BA, O'Connor-Tressel M, Beatty BG, Shively JE, Beatty JD. Artifactual CEA elevation due to human anti-mouse antibodies. Arch Surg 1988;123:1242–6.

  16. 16.

    Hansen HJ, LaFontaine G, Newman ES,et al. Solving the problem of antibody interference in commercial “sandwich”-type immunoassays of carcinoembryonic antigen. Clin Chem 1989;35:146–51.

  17. 17.

    Newman ES, Moskie LA, Duggal RN, Goldenberg DM, Hansen HJ. Murine monoclonal antibody adsorbed onto vinylidene fluoride floccules used to eliminate antibody interference in “sandwich”-type immunoassays. Clin Chem 1989;35:1743–6.

  18. 18.

    Koprowski H, Herlyn D, Lubeck M, DeFreitas E, Sears HF. 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;81:216–9.

  19. 19.

    Bhattacharya-Chatterjee M, Mukerjee S, Biddle W, Foon KA, Kohler H. Murine monoclonal anti-idiotype antibody as a potential network antigen for human carcinoembryonic antigen. J Immunol 1990;145:2758–65.

  20. 20.

    Fagerberg J, Hjelm AL, Ragnhammar P, Frodin JE, Wigzell H, Mellstedt H. Tumor regression in monoclonal antibody-treated patients correlates with the presence of anti-idiotype-reactive T lymphocytes. Cancer Res 1995;55:1824–7.

  21. 21.

    Sun LK, Curtis P, Rakowicz-Szulczynska E,et al. Chimeric antibodies with 17-1A-derived variable and human constant regions. Hybridoma 1986;5(Suppl 1):S17–20.

  22. 22.

    Morrison SL. Transfectomas provide novel chimeric antibodies. Science 1985;229:1202–7.

  23. 23.

    Velders MP, Litvinov SV, Warnaar SO,et al. New chimeric anti-pancarcinoma monoclonal antibody with superior cytotoxicity-mediating potency. Cancer Res 1994;54:1753–9.

  24. 24.

    Hardman N, Gill LL, De Winter RF,et al. Generation of a recombinant mouse-human chimaeric monoclonal antibody directed against human carcinoembryonic antigen. Int J Cancer 1989;44:424–33.

  25. 25.

    Buchegger F, Pelegrin A, Hardman N,et al. Different behaviour of mouse-human chimeric antibody F(ab')2 fragments of IgG1, IgG2 and IgG4 sub-class in vivo. Int J Cancer 1992;50:416–22.

  26. 26.

    LoBuglio AF, Wheeler RH, Trang J,et al. Mouse/human chimeric monoclonal antibody in man: kinetics and immune response. Proc Natl Acad Sci U S A 1989;86:4220–4.

  27. 27.

    Meredith RF, LoBuglio AF, Plott WE,et al. Pharmacokinetics, immune response, and biodistribution of iodine-131-labeled chimeric mouse/human IgG1, k 17-1A monoclonal antibody. J Nucl Med 1991;32:1162–8.

  28. 28.

    Meredith RF, Khazaeli MB, Plott WE,et al. Phase I trial of iodine-131-chimeric B72.3 (human IgG4) in metastatic colorectal cancer. J Nucl Med 1992;33:23–9.

  29. 29.

    Goodman GE, Hellstrom I, Yelton DE,et al. Phase I trial of chimeric (human-mouse) monoclonal antibody L6 in patients with non-small-cell lung, colon, and breast cancer. Cancer Immunol Immunother 1993;36:267–73.

  30. 30.

    Wong JY, Williams LE, Yamauchi DM,et al. Initial experience evaluating 90yttrium-radiolabeled anticarcinoembryonic antigen chimeric T84.66 in a phase I radioimmunotherapy trial. Cancer Res 1995;55(Suppl):5929s-34s.

  31. 31.

    Hosono M, Endo K, Sakahara H,et al. Human/mouse chimeric antibodies show low reactivity with human anti-murine antibodies (HAMA). Br J Cancer 1992;65:197–200.

  32. 32.

    Khazaeli MB, Saleh MN, Liu TP,et al. Pharmacokinetics and immune response of131I-chimeric mouse/human B72.3 (human gamma 4) monoclonal antibody in humans. Cancer Res 1991;51:5461–6.

  33. 33.

    Buchegger F, Mach JP, Pelegrin A,et al. Radiolabeled chimeric anti-CEA monoclonal antibody compared with the original mouse monoclonal antibody for surgically treated colorectal carcinoma. J Nucl Med 1995;36:420–9.

  34. 34.

    Fagerberg J, Ragnhammar P, Liljefors M, Hjelm AL, Mellstedt H, Frodin JE. Humoral anti-idiotypic and anti-anti-idiotypic immune response in cancer patients treated with monoclonal antibody 17-1A. Cancer Immunol Immunother 1996;42:81–7.

  35. 35.

    Steinitz M, Klein G, Koskimies S, Makel O. EB virus-induced B lymphocyte cell lines producing specific antibody. Nature 1977;269:420–2.

  36. 36.

    Olsson L, Kaplan HS. Human-human hybridomas producing monoclonal antibodies of predefined antigenic specificity. Proc Natl Acad Sci U S A 1980;77:5429–31.

  37. 37.

    Del Vecchio S, Carrasquillo JA, Steis R,et al. Imaging of colon cancer with I-131 28A32 human monoclonal antibody. J Nucl Med 1987;28:636 [abstract].

  38. 38.

    Steis RG, Carrasquillo JA, McCabe R,et al. Toxicity, immunogenicity, and tumor radioimmunodetecting ability of two human monoclonal antibodies in patients with metastatic colorectal carcinoma. J Clin Oncol 1990;8:476–90.

  39. 39.

    Koda K, Glassy MC, Chang HR. Generation of human monoclonal antibodies against colon cancer. Arch Surg 1990;125:1591–7.

  40. 40.

    De Jager RL, McCabe RP, Subramanian R,et al. Radio-immunodetection of colorectal carcinoma with a technetium-99m labeled human IgG monoclonal antibody: 88BV59-1: a phase I clinical trial. Proc Am Assoc Cancer Res 1991;32:184.

  41. 41.

    De Jager RL, Abdel-Nabi H, Serafini A,et al. Radioimmunoscintigraphy (RIS) of colorectal cancer with human monoclonal antibody (AB) 88BV59. Antibody Immunoconj Radiophar 1992;5:332.

  42. 42.

    Gulec SA, Serafini AN, Moffat FL,et al. Radioimmunoscintigraphy of colorectal carcinoma using technetium-99m-labeled, totally human monoclonal antibody 88BV59H21-2. Cancer Res 1995;55(Suppl):5774s-6s.

  43. 43.

    Abdel-Nabi H, Evans N, Farrell E,et al. Colorectal carcinoma tumor targeting with elevated human antimouse antibody (HAMA) levels. Antibody Immunoconj Radiophar 1992;5:352.

  44. 44.

    Denton GW, Durrant LG, Hardcastle JD, Austin EB, Sewell HF, Robins RA. Clinical outcome of colorectal cancer patients treated with human monoclonal antidiotypic antibody. Int J Cancer 1994;57:10–4.

  45. 45.

    Chang HR, Chavoshan B, Park H. Human monoclonal antibody SK1-mediated cytotoxicity against colon cancer cells. Dis Colon Rectum 1993;36:1152–7.

  46. 46.

    Erb K, Borup-Christensen P, Ditzel H, Chemnitz J, Haas H, Jensenius JC. Characterization of a human-human hybridoma antibody, C-OU1, directed against a colon tumor-associated antigen. Hybridoma 1992;11:121–34.

  47. 47.

    Ditzel H, Rasmussen JW, Erb K,et al. Tumor detection with131I-labeled human monoclonal antibody COU-1 in patients with suspected colorectal carcinoma. Cancer Res 1993;53:5920–8.

  48. 48.

    Goldenberg DM, Ford EH, Lee RE,et al. Cancer imaging with a new 99m-Tc-antibody method [abstract]. J Nucl Med 1989;15:426.

  49. 49.

    Yokota T, Milenic DE, Whitlow M, Schlom J. Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms. Cancer Res 1992;52:3402–8.

  50. 50.

    Lane DM, Eagle KF, Begent RH,et al. Radioimmunotherapy of metastatic colorectal tumours with iodine-131-labelled antibody to carcinoembryonic antigen: phase I/II study with comparative biodistribution of intact and F(ab')2 antibodies. Br J Cancer 1994;70:521–5.

  51. 51.

    Siccardi AG, Buraggi GL, Callegaro L,et al. Immunoscintigraphy of adenocarcinomas by means of radiolabeled F(ab')2 fragments of an anticarcinoembryonic antigen monoclonal antibody: a multicenter study. Cancer Res 1989;49:3095–103.

  52. 52.

    Serafini AN, Goldenberg DM, Higginbotham-Ford EA,et al. A multicenter trial of cancer imaging with fragments of CEA monoclonal antibodies. J Nucl Med 1989;30:748.

  53. 53.

    Lamki LM, Patt YZ, Rosenblum MG,et al. Metastatic colorectal cancer: radioimmunoscintigraphy with a stabilized In-111-labeled F(ab')2 fragment of an anti-CEA monoclonal antibody. Radiology 1990;174:147–51.

  54. 54.

    Behr TM, Becker WS, Klein MW, Bair HJ, Scheele JR, Wolf FG. Diagnostic accuracy and tumor-targeting kinetics of completeversus fragmented 99mTc-labeled anti-carcinoembryonic antigen antibodies: an intraindividual comparison. Cancer Res 1995;55(Suppl):5786s-93s.

  55. 55.

    Goldenberg DM, Wlodkowski TJ, Sharkey RM,et al. Colorectal cancer imaging with iodine-123-labeled CEA monoclonal antibody fragments. J Nucl Med 1993;34:61–70.

  56. 56.

    Lechner P, Lind P, Binter G, Cesnik H. Anticarcinoembryonic antigen immunoscintigraphy with a 99mTc-Fab' fragment (Immu 4) in primary and recurrent colorectal cancer: a prospective study. Dis Colon Rectum 1993;36:930–5.

  57. 57.

    Moffat FL Jr, Vargas-Cuba RD, Serafini AN,et al. Radioimmunodetection of colorectal carcinoma using technetium-99m-labeled Fab' fragments of the IMMU-4 anti-carcinoembryonic antigen monoclonal antibody. Cancer 1994;73(Suppl):836–45.

  58. 58.

    Murray JL, Rosenblum MG, Zhang HZ,et al. Comparative tumor localization of whole immunoglobulin G anticarcinoembryonic antigen monoclonal antibodies IMMU-4 and IMMU-4 F(ab')2 in colorectal cancer patients. Cancer 1994;73(Suppl):850–7.

  59. 59.

    Gold P, Freedman SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med 1965;122:461–85.

  60. 60.

    Goldenberg DM, DeLand F, Kim E,et al. Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning. N Engl J Med 1978;298:1384–6.

  61. 61.

    Mach JP, Buchegger F, Forni M,et al. Use of radiolabeled monoclonal anti-CEA antibodies for the detection of human carcinomas by external photoscanning and tomoscintigraphy. Immunol Today 1981;2:239–49.

  62. 62.

    Abdel-Nabi HH, Schwartz AN, Higano CS, Wechter DG, Unger MW. Colorectal carcinoma: detection with indium-111 anticarcinoembryonic-antigen monoclonal antibody ZCE-025. Radiology 1987;164:617–21.

  63. 63.

    Behr TM, Sharkey RM, Juweid MI,et al. Factors influencing the pharmacokinetics, dosimetry, and diagnostic accuracy of radioimmunodetection and radioimmunotherapy of carcinoembryonic antigen-expressing tumors. Cancer Res 1996;56:1805–16.

  64. 64.

    Granowska M, Jass JR, Britton KE, Northover JM. A prospective study of the use of 111In-labelled monoclonal antibody against carcino-embryonic antigen in colorectal cancer and of some biological factors affecting its uptake. Int J Colorectal Dis 1989;4:97–108.

  65. 65.

    Abdel-Nabi HH, Schwartz AN, Goldfogel G,et al. Colorectal tumors: scintigraphy with In-111 anti-CEA monoclonal antibody and correlation with surgical, histopathologic, and immunohistochemical findings. Radiology 1988;166:747–52.

  66. 66.

    Wang JY, Tang R, Chiang JM. Value of carcinoembryonic antigen in the management of colorectal cancer. Dis Colon Rectum 1994;37:272–7.

  67. 67.

    Beatty JD, Duda RB, Williams LE,et al. Preoperative imaging of colorectal carcinoma with 111In-labeled anticarcinoembryonic antigen monoclonal antibody. Cancer Res 1986;46:6494–502.

  68. 68.

    Abdel-Nabi HH, Chan HW, Doerr RJ. Indium-labeled anti-colorectal carcinoma monoclonal antibody accumulation in non-tumored tissue in patients with colorectal carcinoma. J Nucl Med 1990;31:1975–9.

  69. 69.

    Bosslet K, Steinstrasser A, Schwarz A,et al. Quantitative considerations supporting the irrelevance of circulating serum CEA for the immunoscintigraphic visualization of CEA expressing carcinomas. Eur J Nucl Med 1988;14:523–8.

  70. 70.

    Hertel A, Baum RP, Lorenz M, Baew-Christow T, Encke A, Hor G. Immunoscintigraphy using a technetium-99m labelled monoclonal anti-CEA antibody in the follow-up of colorectal cancer and other tumours producing CEA. Br J Cancer Suppl 1990;10:34–6.

  71. 71.

    Richman PI, Bodmer WF. Monoclonal antibodies to human colorectal epithelium: markers for differentiation and tumour characterization. Int J Cancer 1987;39:317–28.

  72. 72.

    Durbin H, Young S, Stewart LM,et al. An epitope on carcinoembryonic antigen defined by the clinically relevant antibody PR1A3. Proc Natl Acad Sci U S A 1994;91:4313–7.

  73. 73.

    Granowska M, Britton KE, Mather SJ,et al. Radioimmunoscintigraphy with technetium-99m labelled monoclonal antibody, 1A3, in colorectal cancer. Eur J Nucl Med 1993;20:690–8.

  74. 74.

    Granowska M, Mather SJ, Britton KE. Diagnostic evaluation of 111In and 99mTc radiolabelled monoclonal antibodies in ovarian and colorectal cancer: correlations with surgery. Int J Rad Appl Instrum [B] 1991;18:413–24.

  75. 75.

    Colcher D, Hand PH, Nuti M, Schlom J. A spectrum of monoclonal antibodies reactive with human mammary tumor cells. Proc Natl Acad Sci U S A 1981;78:3199–203.

  76. 76.

    Johnson VG, Schlom J, Paterson AJ, Bennett J, Magnani JL, Colcher D. Analysis of a human tumor-associated glycoprotein (TAG-72) identified by monoclonal antibody B72.3. Cancer Res 1986;46:850–7.

  77. 77.

    Kuroki M, Fernsten PD, Wunderlich D,et al. Serological mapping of the TAG-72 tumor-associated antigen using 19 distinct monoclonal antibodies. Cancer Res 1990;50:4872–9.

  78. 78.

    Esteban JM, Colcher D, Sugarbaker P,et al. Quantitative and qualitative aspects of radiolocalization in colon cancer patients of intravenously administered MAb B72.3. Int J Cancer 1987;39:50–9.

  79. 79.

    Abdel-Nabi H, Doerr RJ, Chan HW, Balu D, Schmelter RF, Maguire RT. In-111-labeled monoclonal antibody immunoscintigraphy in colorectal carcinoma: safety, sensitivity, and preliminary clinical results. Radiology 1990;175:163–71.

  80. 80.

    Winzelberg GG, Grossman SJ, Rizk S,et al. Indium-111 monoclonal antibody B72.3 scintigraphy in colorectal cancer: correlation with computed tomography, surgery, histopathology, immunohistology, and human immune response. Cancer 1992;69:1656–63.

  81. 81.

    Kostakoglu L, Divgi CR, Hilton S,et al. Preselection of patients with high TAG-72 antigen expression leads to targeting of 94 percent of known metastatic tumor sites with monoclonal antibody I-131-CC49. Cancer Invest 1994;12:551–8.

  82. 82.

    Guadagni F, Roselli M, Cosimelli M,et al. TAG-72 (CA 72-4 assay) as a complementary serum tumor antigen to carcinoembryonic antigen in monitoring patients with colorectal cancer. Cancer 1993;72:2098–106.

  83. 83.

    Muraro R, Kuroki M, Wunderlich D,et al. Generation and characterization of B72.3 second generation monoclonal antibodies reactive with the tumor-associated glycoprotein 72 antigen. Cancer Res 1988;48:4588–96.

  84. 84.

    Arnold MW, Schneebaum S, Berens A,et al. Intraoperative detection of colorectal cancer with radioimmunoguided surgery and CC49, a second-generation monoclonal antibody. Ann Surg 1992;216:627–32.

  85. 85.

    Schlom J, Eggensperger D, Colcher D,et al. Therapeutic advantage of high-affinity anticarcinoma radioimmunoconjugates. Cancer Res 1992;52:1067–72.

  86. 86.

    Gallinger S, Reilly RM, Kirsh JC,et al. Comparative dual label study of first and second generation antitumor-associated glycoprotein-72 monoclonal antibodies in colorectal cancer patients. Cancer Res 1993;53:271–8.

  87. 87.

    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;76:1438–52.

  88. 88.

    Steplewski Z, Chang TH, Herlyn M, Koprowski H. Release of monoclonal antibody-defined antigens by human colorectal carcinoma and melanoma cells. Cancer Res 1981;41:2723–7.

  89. 89.

    Herlyn D, Sears H, Iliopoulos D,et al. Anti-idiotypic antibodies to monoclonal antibody CO17-1A. Hybridoma 1986;5(Suppl 1):S51–8.

  90. 90.

    Gottlinger HG, Funke I, Johnson JP, Gokel JM, Riethmuller G. The epithelial cell surface antigen 17-1A, a target for antibody-mediated tumor therapy: its biochemical nature, tissue distribution and recognition by different monoclonal antibodies. Int J Cancer 1986;38:47–53.

  91. 91.

    Herlyn D, Herlyn M, Ross AH, Ernst C, Atkinson B, Koprowski H. Efficient selection of human tumor growth-inhibiting monoclonal antibodies. J Immunol Methods 1984;73:157–67.

  92. 92.

    Herlyn DM, Steplewski Z, Herlyn MF, Koprowski H. Inhibition of growth of colorectal carcinoma in nude mice by monoclonal antibody. Cancer Res 1980;40:717–21.

  93. 93.

    Herlyn D, Somasundaram R, Zaloudik J,et al. Anti-idiotype and recombinant antigen in immunotherapy of colorectal cancer. Cell Biophys 1994;24–25:143–53.

  94. 94.

    Woo DV, Li D, Mattis JA, Steplewski Z. Selective chromosomal damage and cytotoxicity of125I-labeled monoclonal antibody 17-1a in human cancer cells. Cancer Res 1989;49:2952–8.

  95. 95.

    Meredith RF, Khazaeli MB, Plott WE,et al. Initial clinical evaluation of iodine-125-labeled chimeric 17-1A for metastatic colon cancer. J Nucl Med 1995;36:2229–33.

  96. 96.

    Riethmuller G, Schneider-Gadicke E, Schlimok G,et al. Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma. German Cancer Aid 17-1A Study Group [see comments]. Lancet 1994;343:1177–83.

  97. 97.

    Leinsinger G, Kirsch CM, Denecke H, Pletzer G. Immunoscintigraphy using SPECT and I-131 labeled monoclonal antibodies to CEA/CA 19-9 in the follow-up of colorectal cancer. Antib Immunoconj Radiopharm 1991;4:577–85.

  98. 98.

    Epenetos AA, Nimmon CC, Arklie J,et al. Detection of human cancer in an animal model using radio-labelled tumour-associated monoclonal antibodies. Br J Cancer 1982;46:1–8.

  99. 99.

    Welt S, Divgi CR, Kemeny N,et al. Phase I/II study of iodine 131-labeled monoclonal antibody A33 in patients with advanced colon cancer. J Clin Oncol 1994;12:1561–71.

  100. 100.

    Breitz HB, Weiden PL, Vanderheyden JL,et al. Clinical experience with rhenium-186-labeled monoclonal antibodies for radioimmunotherapy: results of phase I trials [see comments]. J Nucl Med 1992;33:1099–109.

  101. 101.

    Bell SM, Scott N, Cross D,et al. Prognostic value of p53 overexpression and c-Ki-ras gene mutations in colorectal cancer. Gastroenterology 1993;104:57–64.

  102. 102.

    Kressner U, Lindmark G, Gerdin B, Pahlman L, Glimelius B. Immunohistological p53 staining is of limited value in the staging and prognostic prediction of colorectal cancer. Anticancer Res 1996;16:951–7.

  103. 103.

    Davidson BR, Young H, Waddington WA,et al. Preoperative imaging of colorectal cancers: targeting the epithelial membrane antigen with a radiation-labeled monoclonal antibody. Cancer 1992;69:620–5.

  104. 104.

    Rodriguez-Bigas MA, Bakshi S, Stomper P, Blumenson LE, Petrelli NJ. 99mTc-IMMU-4 monoclonal antibody scan in colorectal cancer: a prospective study. Arch Surg 1992;127:1321–4.

  105. 105.

    Beatty JD, Williams LE, Yamauchi D,et al. Presurgical imaging with indium-labeled anti-carcinoembryonic antigen for colon cancer staging. Cancer Res 1990;50(Suppl):922s-6s.

  106. 106.

    Bock E, Becker W, Scheele J, Wolf F. Diagnostic accuracy of 99mTc-anti-CEA immunoscintigraphy in patients with liver metastases from colorectal carcinoma. Nuklearmedizin 1992;31:80–3.

  107. 107.

    Behr T, Becker W, Hannappel E, Goldenberg DM, Wolf F. Targeting of liver metastases of colorectal cancer with IgG, F(ab')2, and Fab' anti-carcinoembryonic antigen antibodies labeled with 99mTc: the role of metabolism and kinetics. Cancer Res 1995;55(Suppl):5777s-85s.

  108. 108.

    Bischof-Delaloye A, Delaloye B, Buchegger F,et al. Clinical value of immunoscintigraphy in colorectal carcinoma patients: a prospective study. J Nucl Med 1989;30:1646–56.

  109. 109.

    Beatty JD, Hyams DM, Morton BA,et al. Impact of radiolabeled antibody imaging on management of colon cancer. Am J Surg 1989;157:13–9.

  110. 110.

    Corbisiero RM, Yamauchi DM, Williams LE, Esteban JM, Odom-Maryon T, Beatty JD. Colomparison of immunoscintigraphy and computerized tomography in identifying colorectal cancer: individual lesion analysis. Cancer Res 1991;51:5704–11.

  111. 111.

    Moffat FL Jr, Pinsky CM, Hammershaimb L,et al. Clinical utility of external immunoscintigraphy with the IMMU-4 technetium-99m Fab' antibody fragment in patients undergoing surgery for carcinoma of the colon and rectum: results of a pivotal, phase III trial. The Immunomedics Study Group. J Clin Oncol 1996;14:2295–305.

  112. 112.

    Divgi CR, McDermott K, Griffin TW,et al. Lesion-by-lesion comparison of computerized tomography and indium-111-labeled monoclonal antibody C110 radio-immunoscintigraphy in colorectal carcinoma: a multicenter trial. J Nucl Med 1993;34:1656–61.

  113. 113.

    Scott AM, Macapinlac HA, Divgi CR,et al. Clinical validation of SPECT and CT/MRI image registration in radiolabeled monoclonal antibody studies of colorectal carcinoma. J Nucl Med 1994;35:1976–84.

  114. 114.

    Dominguez JM, Wolff BG, Nelson H, Forstrom LA, Mullan BP.111In-CYT-103 scanning in recurrent colorectal cancer-does it affect standard management? Dis Colon Rectum 1996;39:514–9.

  115. 115.

    Cornelius E, West B, Forstrom L, Ferguson D, Schecter L. The lymph node: immunologic functions relevant to radioimmunodiagnosis (RAID) and radioimmunoguided surgery (RIGS). J Nucl Med 1994;35:275P.

  116. 116.

    Duda RB, Zimmer AM, Rosen ST,et al. Radioimmune localization of occult carcinoma. Arch Surg 1990;125:866–70.

  117. 117.

    Doerr RJ, Abdel-Nabi H, Merchant B. Indium 111 ZCE-025 immunoscintigraphy in occult recurrent colorectal cancer with elevated carcinoembryonic antigen level. Arch Surg 1990;125:226–9.

  118. 118.

    Halpern SE, Dillman RO, Amox D,et al. Detection of occult tumor using indium 111-labeled anticarcinoembryonic antigen antibodies. Arch Surg 1992;127:1094–100.

  119. 119.

    Patt YZ, Podoloff DA, Curley S,et al. Monoclonal antibody imaging in patients with colorectal cancer and increasing levels of serum carcinoembryonic antigen: experience with ZCE-025 and IMMU-4 monoclonal antibodies and proposed directions for clinical trials. Cancer 1993;71(Suppl):4293–7.

  120. 120.

    Petersen BM Jr, Bass BL, Bates HR, Chandeysson PL, Harmon JW. Use of the radiolabeled murine monoclonal antibody, 111In-CYT-103, in the management of colon cancer. Am J Surg 1993;165:137–42.

  121. 121.

    Gasparini M, Buraggi GL, Regalia E, Maffioli L, Balzarini L, Gennari L. Comparison of radioimmunodetection with other imaging methods in evaluating local relapses of colorectal carcinoma. Cancer 1994;73(Suppl):846–9.

  122. 122.

    Paganelli G, Magnani P, Zito F,et al. Three-step monoclonal antibody tumor targeting in carcinoembryonic antigen-positive patients. Cancer Res 1991;51:5960–6.

  123. 123.

    Martin DT, Hinkle GH, Tuttle S,et al. Intraoperative radioimmunodetection of colorectal tumor with a hand-held radiation detector. Am J Surg 1985;150:672–5.

  124. 124.

    Dawson PM, Blair SD, Begent RH, Kelly AM, Boxer GM, Theodorou NA. The value of radioimmunoguided surgery in first and second look laparotomy for colorectal cancer. Dis Colon Rectum 1991;34:217–22.

  125. 125.

    Burak WE Jr, Schneebaum S, Kim JA,et al. Pilot study evaluating the intraoperative localization of radiolabeled monoclonal antibody CC83 in patients with metastatic colorectal carcinoma [see comments]. Surgery 1995;118:103–8.

  126. 126.

    Sardi A, Workman M, Mojzisik C, Hinkle G, Nieroda C, Martin EW Jr. Intra-abdominal recurrence of colorectal cancer detected by radioimmunoguided surgery (RIGS system). Arch Surg 1989;124:55–9.

  127. 127.

    Cohen AM, Martin EW Jr, Lavery I,et al. Radioimmunoguided surgery using iodine 125 B72.3 in patients with colorectal cancer. Arch Surg 1991;126:349–52.

  128. 128.

    Schneebaum S, Arnold MW, Houchens DP,et al. The significance of intraoperative periportal lymph node metastasis identification in patients with colorectal carcinoma. Cancer 1995;75:2809–17.

  129. 129.

    Cote RJ, Houchens DP, Hitchcock CL,et al. Intraoperative detection of occult colon cancer micrometastases using 125 I-radiolabled monoclonal antibody CC49. Cancer 1996;77:613–20.

  130. 130.

    Howell R, Hawley PR, Granowska M, Morris G, Britton KE. Peroperative radioimmunodetection, PROD, of colorectal cancer using 99m-Tc PR1A3 monoclonal antibody. Tumori 1995;81(Suppl):107–8.

  131. 131.

    Curtet C, Vuillez JP, Daniel G,et al. Feasibility study of radioimmunoguided surgery of colorectal carcinomas using indium-111 CEA-specific monoclonal antibody. Eur J Nucl Med 1990;17:299–304.

  132. 132.

    Moffat FL Jr, Vargas-Cuba RD, Serafini AN,et al. Preoperative scintigraphy and operative probe scintimetry of colorectal carcinoma using technetium-99m-88BV59. J Nucl Med 1995;36:738–45.

  133. 133.

    Nieroda CA, Mojzisik C, Hinkle G, Thurston MO, Martin EW Jr. Radioimmunoguided surgery (RIGS) in recurrent colorectal cancer. Cancer Detect Prev 1991;15:225–9.

  134. 134.

    LoBuglio AF, Saleh M, Peterson L,et al. Phase I clinical trial of CO17-1A monoclonal antibody. Hybridoma 1986;5(Suppl 1):S117–23.

  135. 135.

    Douillard JY, Lehur PA, Vignoud J,et al. Monoclonal antibodies specific immunotherapy of gastrointestinal tumors. Hybridoma 1986;5(Suppl 1):S139–49.

  136. 136.

    Sears HF, Herlyn D, Steplewski Z, Koprowski H. Phase II clinical trial of a murine monoclonal antibody cytotoxic for gastrointestinal adenocarcinoma. Cancer Res 1985;45:5910–3.

  137. 137.

    Verrill H, Goldberg M, Rosenbaum R,et al. Clinical trial of Wistar Institute 17-1A monoclonal antibody in patients with advanced gastrointestinal adenocarcinoma: a preliminary report. Hybridoma 1986;5(Suppl 1):S175–83.

  138. 138.

    LoBuglio AF, Saleh MN, Lee J,et al. Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A. I. Clinical aspects. J Natl Cancer Inst 1988;80:932–6.

  139. 139.

    Mellstedt H, Frodin JE, Masucci G,et al. Monoclonal antibodies (MAb 17-1A) for the treatment of patients with metastatic colorectal carcinomas. Acta Chir Scand Suppl 1989;549:63–70.

  140. 140.

    Pullyblank AM, Guillou PJ, Monson JR. m17-1A-, c17-1A-and cSF25-mediated antibody-dependent cell-mediated cytotoxicity in patients with advanced cancer. Br J Cancer 1994;70:753–8.

  141. 141.

    Hagan PL, Halpern SE, Dillman RO,et al. Tumor size: effect on monclonal antibody uptake in tumor models. J Nucl Med 1986;27:422–7.

  142. 142.

    Jain RK. Delivery of molecular medicine to solid tumors. Science 1996;271:1079–80.

  143. 143.

    Baxter LT, Jain RK. Pharmacokinetic analysis of the microscopic distribution of enzyme-conjugated antibodies and prodrugs: comparison with experimental data. Br J Cancer 1996;73:447–56.

  144. 144.

    Sears HF, Herlyn D, Steplewski Z, Koprowski H. Initial trial use of murine monoclonal antibodies as immunotherapeutic agents for gastrointestinal adenocarcinoma. Hybridoma 1986;5(Suppl 1):S109–15.

  145. 145.

    Weiner LM, Steplewski Z, Koprowski H, Sears HF, Litwin S, Comis RL. Biologic effects of gamma interferon pre-treatment followed by monoclonal antibody 17-1A administration in patients with gastrointestinal carcinoma. Hybridoma 1986;5(Suppl 1):S65–77.

  146. 146.

    Frodin JE, Harmenberg U, Biberfeld P,et al. Clinical effects of monoclonal antibodies (MAb 17-1A) in patients with metastatic colorectal carcinomas. Hybridoma 1988;7:309–21.

  147. 147.

    Weiner LM, Moldofsky PJ, Gatenby RA,et al. Antibody delivery and effector cell activation in a phase II trial of recombinant gamma-interferon and the murine monoclonal antibody CO17-1A in advanced colorectal carcinoma. Cancer Res 1988;48:2568–73.

  148. 148.

    Riethmuller G, Holz E, Schlimok G,et al. Monoclonal antibody (MAB) adjuvant therapy of Dukes' C colorectal carcinoma: 7-year update of a prospective randomized trial. Proc Am Soc Clin Oncol 1996;5:444.

  149. 149.

    Moertel CG, Fleming TR, Macdonald JS,et al. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 1990;322:352–8.

  150. 150.

    Moertel CG, Fleming TR, Macdonald JS,et al. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med 1995;122:321–6.

  151. 151.

    Krook JE, Moertel CG, Gunderson LL,et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma [see comments]. N Engl J Med 1991;324:709–15.

  152. 152.

    Schneider-Gadicke E, Riethmuller G. Prevention of manifest metastasis with monoclonal antibodies: a novel approach to immunotherapy of solid tumours [Review]. Eur J Cancer 1995;31A:1326–30.

  153. 153.

    Schöber C, Schultke M, Schlimok G,et al. Open label pitol study of monoclonal antibody 17-1A in combination with 5-Fluorouracil/Levamisole or 5FU/Folinic Acid in patients with advanced colorectal cancer [abstract]. Proc Am Soc Clin Oncol 1996;15:229.

  154. 154.

    Markoe AM, Brady LW, Woo D,et al. Treatment of gastrointestinal cancer using monoclonal antibodies. In: Vaeth JM, Meyer JL, eds. The present and future role of monoclonal antibodies in the management of cancer. Vol. 24. Basel: Karger, 1990:214–24.

  155. 155.

    Rosenblum MG, Macey D, Podoloff D,et al. A Phase I pharmacokinetic, toxicity and dosimetry study of131I-labeled IMMU-4 F(ab')2 in patients with advanced colorectal carcinoma. Antibody Immunoconj Radiopharm 1993;6:239.

  156. 156.

    Murray JL, Macey DJ, Kasi LP,et al. Phase II radioimmunotherapy trial with131I-CC49 in colorectal cancer. Cancer 1994;73(Suppl):1057–66.

  157. 157.

    Divgi CR, Scott AM, Dantis L,et al. Phase I radioimmunotherapy trial with iodine-131-CC49 in metastatic colon carcinoma. J Nucl Med 1995;36:586–92.

  158. 158.

    Yu B, Carrasquillo J, Milenic D,et al. Phase I trial of iodine 131-labeled COL-1 in patients with gastrointestinal malignancies: influence of serum carcinoembryonic antigen and tumor bulk on pharmacokinetics. J Clin Oncol 1996;14:1798–809.

  159. 159.

    Buchegger F, Rojas A, Delaloye AB,et al. Combined radioimmunotherapy and radiotherapy of human colon carcinoma grafted in nude mice. Cancer Res 1995;55:83–9.

  160. 160.

    Tschmelitsch J, Welt S, Barendswaard E, Yao T-J, Cohen A, Old LJ. Enhanced antitumor activity of combination radioimmunotherapy (131I-monoclonal antibody A33) with chemotherapy (fluorouracil) [abstract]. Proc Am Assoc Cancer Res 1996;37:469.

  161. 161.

    Ballantyne KC, Perkins AC, Pimm MV,et al. Biodistribution of a monoclonal antibody-methotrexate conjugate (791T/36-MTX) in patients with colorectal cancer. Int J Cancer Suppl 1988;2:103–8.

  162. 162.

    Takahashi T, Yamaguchi T, Kitamura K,et al. Clinical application of monoclonal antibody-drug conjugates for immunotargeting chemotherapy of colorectal carcinoma. Cancer 1988;61:881–8.

  163. 163.

    Takahashi T, Yamaguchi T, Kitamura K, Noguchi A, Honda M, Otsuji E. Follow-up study of patients treated with monoclonal antibody-drug conjugate: report of 77 cases with colorectal cancer. Jpn J Cancer Res 1993;84:976–81.

  164. 164.

    Byers VS, Rodvien R, Grant K,et al. Phase I study of monoclonal antibody-ricin A chain immunotoxin XomaZyme-791 in patients with metastatic colon cancer. Cancer Res 1989;49:6153–60.

  165. 165.

    LoRusso PM, Lomen PL, Redman BG, Poplin E, Bander JJ, Valdivieso M. Phase I study of monoclonal antibody-ricin A chain immunoconjugate Xomazyme-791 in patients with metastatic colon cancer. Am J Clin Oncol 1995;18:307–12.

  166. 166.

    Zalcberg JR, Pietersz G, Toohey B,et al. A phase I/II study of the intralesional injection of ricin-monoclonal antibody conjugates in patients with hepatic metastases. Eur J Cancer 1994;30A:1227–31.

  167. 167.

    Litton MJ, Dohlsten M, Lando PA,et al. Antibody-targeted superantigen therapy induces tumorinfiltrating lymphocytes, excessive cytokine production, and apoptosis in human colon carcinoma. Eur J Immunol 1996;26:1–9.

  168. 168.

    Giantonio BJ, Weiner LM, Alpaugh RK,et al. Superantigen based immunotherapy: a phase I trial of the staphylococcal enterotoxin a (SEA) with advanced pancreatic and colorectal cancer [abstract]. Proc Am Soc Clin Oncol 1996;15:443.

  169. 169.

    Penna C, Dean PA, Nelson H. Antitumor x anti-CD3 bifunctional antibodies redirect T-cells activated in vivo with staphylococcal enterotoxin B to neutralize pulmonary metastases. Cancer Res 1994;54:2738–43.

  170. 170.

    Nieken J, Vershueren RC, Timens W, De Ley L, Mulder NH. Intratumoral (i.t.) bispecific monoclonal antibody (bsmAb) in the treatment of colorectal cancer [abstract]. Proc Am Assoc Cancer Res 1995;36:496.

  171. 171.

    Liesveld JL, Frediani KE, Winslow JM, Duerst RE, Abboud CN. Cytokine effects and role of adhesive proteins and Fc receptors in human macrophage-mediated antibody dependent cellular cytotoxicity. J Cell Biochem 1991;45:381–90.

  172. 172.

    Ragnhammar P, Fagerberg J, Frodin JE,et al. Effect of monoclonal antibody 17-1A and GM-CSF in patients with advanced colorectal carcinoma-long-lasting, complete remissions can be induced. Int J Cancer 1993;53:751–8.

  173. 173.

    Ragnhammar P, Fagerberg J, Frodin JE, Wersall P, Hansson LO, Mellstedt H. Granulocyte/macrophagecolony-stimulating factor augments the induction of antibodies, especially anti-idiotypic antibodies, to therapeutic monoclonal antibodies. Cancer Immunol Immunother 1995;40:367–75.

  174. 174.

    Saleh MN, LoBuglio AF, Wheeler RH,et al. A phase II trial of murine monoclonal antibody 17-1A and interferon-gamma: clinical and immunological data. Cancer Immunol Immunother 1990;32:185–90.

  175. 175.

    Saleh MN, Khazaeli MB, Wheeler RH,et al. Phase II trial of murine monoclonal antibody D612 combined with recombinant human monocyte colonystimulating factor (rhM-CSF) in patients with metastatic gastrointestinal cancer. Cancer Res 1995;55:4339–46.

  176. 176.

    Foon KA, Chatterjee S, Chakraborty M, John WJ, Sherratt A, Bhattacharaya-Chatterjee M. Anti-idiotype antibody vaccine (3H1) that mimics the carcinoembryonic antigen (CEA) as adjuvant treatment [abstract]. Proc Am Soc Clin Oncol 1996;15:554.

  177. 177.

    Pervin S, Sherratt A, Wang H-T,et al. Proliferation of T-cells from colon cancer patients by peptides based on the structure of an anti-idiotype antibody mimicking CEA. Proc Am Assoc Cancer Res 1996;37:473–474.

  178. 178.

    Ciardiello F, Damiano V, Bianco C,et al. Antitumor activity of anti-epidermal growth factor receptor (EGFR) 225 monoclonal antibody (mAb) in combination with 8-CI-cAMP in human colon cancer xenografts. Proc Am Soc Clin Oncol 1996;15:499.

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Correspondence to Dr. Heidi Nelson M.D..

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Stocchi, L., Nelson, H. Diagnostic and therapeutic applications of monoclonal antibodies in colorectal cancer. Dis Colon Rectum 41, 232–250 (1998).

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Key words

  • Monoclonal antibody
  • Colorectal cancer
  • Immunoscintigraphy
  • Immunotherapy