Advertisement

Drug immunoconjugates

  • Malek Safa
  • Kenneth A. Foon
  • Robert K. Oldham
Chapter

Abstract

Monoclonal antibodies and their immunoconjugates represent one of the first practical methods for the selective treatment of cancer [42]. Monoclonal antibody technology now allows for the generation of antibodies or ‘cocktails’ of antibodies that have some selectivity for cancer tissue as compared with the normal tissue oforigin. These antibodies can be tested as unconjugated antibody alone or in conjunction with effector cells. The ‘signal strength’ of the antibody may be made more powerful by conjugating antibody to drugs, toxins, biologicals, and radioisotopes with different mechanisms of action and different levels of potency. This chapter will focus on the use of drug immunoconjugates for cancer treatment.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Andrew AM, Pim MV, Perkins AC, Baldwin RW. Comparative imaging and biodistribution studies with an anti-CEA monoclonal antibody and its F(ab)2 and Fab fragments in mice with colon carcinoma xenografts. Eur J Nucl Med 1986; 12: 168–75.PubMedCrossRefGoogle Scholar
  2. 2.
    Avner B, Avner BP, Gaydos B et al. Characterization of a method using viable human target cells as the solid phase in a cell concentration fluorescence immunoassay (CCFIA) for screening of monoclonal antibodies and hybridoma supernatants. J Immunol Methods 1988; 113: 123–35.PubMedCrossRefGoogle Scholar
  3. 3.
    Avner BP, Liao SK, Avner B et al. Therapeutic murine monoclonal antibodies developed for individual cancer patients. J Biol Response Modif 1989; 8: 25–36.Google Scholar
  4. 4.
    Avner B, Swindell L, Sharp E et al. Evaluation and clinical relevance of patient immune responses to intravenous therapy with murine monoclonal antibodies conjugated to adriamycin. Mol Biother 1991; 3: 14–21.PubMedGoogle Scholar
  5. 5.
    Bagshawe KD. Antibody directed enzymes activate pro-drugs at tumor site. Order SE, ed. Antibody Immunoconj Radiopharm 1990; 3: 60–5Google Scholar
  6. 6.
    Ballantyne KC, Perkins AC, Pimm MV et al. Localization of monoclonal antibody-drug conjugate 791T/36-methotrexate in colorectal cancer. STS Abstr 1986; no. 88.Google Scholar
  7. 7.
    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.PubMedCrossRefGoogle Scholar
  8. 8.
    Ballou B, Jaffe R, Persiani S et al. Tissue localization of methotrexate-monoclonal-IgM immunoconjugates: antiSSEA-1 and MOPC 104E in mouse teratocarcinomas and normal tissues. Cancer Immunol Immunother 1992; 35: 251–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Belles-Isles M, Page M. In vitro activity of daunomycin antialpha-fetoprotein conjugate on mouse hepatoma cell. Cancer (Phila) 1980; 41: 841–5.Google Scholar
  10. 10.
    Carrasquillo JA, Abrams PG, Schroff R et al. Effect of antibody dose on the imaging and biodistribution of indium-111 9.2.27 anti-melanoma monoclonal antibody. J Nucl Med 1988; 29: 39–47.PubMedGoogle Scholar
  11. 11.
    Carrasquillo JA, Bunn PA, Kennan AM et al. Radioimmunodetection of cutaneous T-cell lymphoma with 111In-T101 monoclonal antibody. N Engl J Med 1986; 315: 673–80.PubMedCrossRefGoogle Scholar
  12. 12.
    Carter G, White P, Fernie M et al. Enhanced antitumour effect of liposomal daunorubicin using antibody-phospholipase C conjugates or fusion protein. Int J Oncol 1998; 13: 819–25.PubMedGoogle Scholar
  13. 13.
    Chari RJ, Gross JL, Goldmacher VS et al. Conjugates of monoclonal antibodies and cytotoxic macrolide drugs: potent, target specific antibody-drug conjugates. Antibody Immunoconj Radiopharm 1990; 3: 64.Google Scholar
  14. 14.
    Chari VJ, Martell BA, Gross JL et al. Immunoconjugates containing novel maytansinoids: promising anticancer drugs. Cancer Res 1992; 52: 127–31.PubMedGoogle Scholar
  15. 15.
    Dillman RO. Monoclonal antibodies in the treatment of cancer. Crit Rev Hematol Oncol 1984; 1: 357–86.CrossRefGoogle Scholar
  16. 16.
    Dillman RO. Monoclonal antibodies for treating cancer. Ann Intern Med 1989; 111: 592–603.PubMedCrossRefGoogle Scholar
  17. 17.
    Dillman RO. Human antimouse and antiglobulin responses to monoclonal antibodies. Antibody Immunoconj Radiopharm 1990; 3: 1–16.Google Scholar
  18. 18.
    Dillman RO, Shawler DL, Sobol RE. Murine monoclonal antibody therapy in two patients with chronic lymphocytic leukemia. Blood 1982; 59: 1036–46.PubMedGoogle Scholar
  19. 19.
    Dillman RO, Shawler DL, Johnson DE et al. Preclinical trials with combinations and conjugates of T101 and doxorubicin. Cancer Res 1986; 46: 4886–91.PubMedGoogle Scholar
  20. 20.
    Dillman RO, Johnson DE, Shawler DL. Comparisons of drug and toxin immunoconjugates. Antibody Immunoconj Radiopharm 1988; 1: 65–77.Google Scholar
  21. 21.
    Dillman RO, Johnson DE, Shawler DL, Koziol JA. Superiority of an acid-labile daunorubicin-monoclonal antibody immunoconjugate compared to free drug. Cancer Res 1988; 48: 6097–102.PubMedGoogle Scholar
  22. 22.
    Embleton MJ. Drug targeting by monoclonal antibodies. Br J Cancer 1987; 55: 227–31.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Elias DJ, Kline LE, Robbins BA et al. Monoclonal antibody KS1/4-methotrexate immunoconjugate studies in non-small cell lung carcinoma. Am J Respir Crit Care Med 1994; 150: 1114–22.PubMedCrossRefGoogle Scholar
  24. 24.
    Fidler IJ, Poste G. The cellular heterogeniety of malignant neoplasms: implications for adjuvant chemotherapy. Semin Oncol 1985; 12: 207–21.PubMedGoogle Scholar
  25. 25.
    Foon KA, Bernhard MI, Oldham RK. Monoclonal antibody therapy: assessment by animal tumor models. J Biol Response Modif 1982; 1: 277–304.Google Scholar
  26. 26.
    Foon KA, Bunn PA, Schroff RW et al. Monoclonal antibody therapy of chronic lymphocytic leukemia and cutaneous T-cell lymphoma: preliminary observations. In: Boss BD, Langman RE, Trowbridge IS, Dudlbecco R, eds. Monoclonal Antibody and Cancer. New York: Academic Press, 1983: 39–52.Google Scholar
  27. 27.
    Ford CH, Newman CE, Johnson JR et al. Localization and toxicity study of a vindesine-anti-CEA conjugate in patients with advanced cancer. Br J Cancer 1983; 47: 35–42.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Krizan Z, Murray JL, Hersh EM et al. Increased labeling of human melanoma cells in vitro using combinations of monoclonal antibodies recognizing separate cell surface antibenic determinants. Cancer Res 1985; 45: 4904–9.PubMedGoogle Scholar
  29. 29.
    Ghose T, Blair AH. Antibody linked cytotoxic agents in the treatment of cancer: current status and future prospects. J Natl Cancer Inst 1978; 61: 657–76.PubMedGoogle Scholar
  30. 30.
    Ghose T, Blair AH, Uadia P et al. Antibodies as carriers of cancer chemotherapeutic agents. Ann NY Acad Sci 1985; 446: 213–27.PubMedCrossRefGoogle Scholar
  31. 31.
    Goldenberg DM, DeLand FH. History and status of tumor imaging with radiolabled antibodies. J Biol Response Modif 1982; 1: 121–36.Google Scholar
  32. 32.
    Goodman GE, Beauimer P, Hellstrom I et al. Phase I trial of murine monoclonal antibodies in patients with advanced melanoma. J Clin Oncol 1984; 3: 340–52.Google Scholar
  33. 33.
    Guillemard V, Saragovi HU. Taxane-antibody conjugates afford potent cytotoxicity, enhanced solubility, and tumor target selectivity. Cancer Res 2001; 61: 694–9.PubMedGoogle Scholar
  34. 34.
    Hellstrom I, Hellstrom KE, Siegall CB, Trail PA. Immunoconjugates and immunotoxins for therapy of carcinomas. In: August JT, Anders MW, Murad F, Coyle JT, eds. Advances in Pharmacology, vol. 33, 1st edn. San Diego: Academic Press, 1995: 349–88.CrossRefGoogle Scholar
  35. 35.
    Hurwitz E, Levy R, Maron K et al. The covalent binding of daunomycin and Adriamycin to antibodies with retention of both drug antibody activities. Cancer Res 1975; 3: 1175–81.Google Scholar
  36. 36.
    Hwang KM, Foon KA, Cheung PH et al. Selective antitumor effect on L-10 hepato-carcinoma cells of a potent immunoconjugate composed of the A chain of abrin and monoclonal antibody to a hepatoma-associated antigen. Cancer Res 1984; 44: 4578–86.PubMedGoogle Scholar
  37. 37.
    Hwang KM, Foon KA, Cheung PH et al. Selective antitumor effect of a potent immunoconjugate composed of the A chain of abrin and monoclonal antibody to a hepatola associate antigen. Cancer Res 1984; 44: 4578–86.PubMedGoogle Scholar
  38. 38.
    Hwang KM, Keenan AM, Frincke J et al. Dynamic interaction of 111 indium-labeled monoclonal antibodies with surface of solid tumors visualized in vivo by external scintigraphy. J Nat Cancer Inst 1986; 76: 849–55.PubMedGoogle Scholar
  39. 39.
    Johnson JR, Ford CMG, Newman E et al. A vindesine-antiCEA conjugate cytotoxic for human cancer cell in vitro. Br J Cancer 1981; 44: 472–7.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Larson SM, Brown JP, Wright PW et al. Imaging of melanoma with I-labeled monoclonal antibodies. J Nucl Med 1983; 24: 123–9.PubMedGoogle Scholar
  41. 41.
    Lee FH, Hwang KM. Antibodies as specific carriers for chemotherapeutic agents. Cancer Chemother Pharmacol 1979; 3: 17–25.PubMedCrossRefGoogle Scholar
  42. 42.
    Levy R. Biologicals for cancer treatment: Monoclonal antibodies. Hosp Pract 1985; 15: 67–92.Google Scholar
  43. 43.
    Liao SK, Meranda C, Avner BP et al. Immunohistochemical phenotyping of human solid tumors with monoclonal antibodies in devising biotherapeutic strategies. Cancer Immunol Immunother 1989; 28: 77–86.PubMedCrossRefGoogle Scholar
  44. 44.
    McLauglin P, Grillo-Lopez AJ, Link BK et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 1998; 16: 2825–33.Google Scholar
  45. 45.
    Miller RA, Levy R. Response of cutaneous T-cell lymphoma to therapy with hybridoma monoclonal antibody. Lancet 1981; 2: 226–30.PubMedCrossRefGoogle Scholar
  46. 46.
    Miller RA, Maloney DG, Warnke R et al. Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med 1982; 306: 517–22.PubMedCrossRefGoogle Scholar
  47. 47.
    Newton DL, Hansen HJ, Mikulski SM et al. Potent and specific antitumor effects of an anti-CD22-targeted cytotoxic ribonuclease: potential for the treatment of non-Hodgkin lymphoma. Blood 2001; 97: 528–35.PubMedCrossRefGoogle Scholar
  48. 48.
    Ogden JR, Leung K, Kundra SA et al. Immunoconjugates of doxorubicin and murine antihuman breast carcinoma monoclonal antibodies prepared via an n-hydroxysuccinimide active ester intermediate of cis-aconityl-doxorubicin: preparation and in vitro cytotoxicity. Mol Biother 1989; 1: 170–4.PubMedGoogle Scholar
  49. 49.
    Ohkawa K, Hibi N, Tsukada Y. Evaluation of a conjugate of purified antibodies against human AFP-dextran-daunorubicin to human AFP-producing yolk sac tumor cell lines. Cancer Immunol Immunother 1986; 22: 81–6.PubMedCrossRefGoogle Scholar
  50. 50.
    Oldham RK. Monoclonal antibodies in cancer therapy. J Clin Oncol 1983; 1: 582–90.PubMedGoogle Scholar
  51. 51.
    Oldham RK. Biologicals: new horizons in pharmaceutical development. J Biol Response Modif 1983; 2: 199–206.Google Scholar
  52. 52.
    Oldham RK. Biologicals and biological response modifiers: fourth modality of cancer treatment. Cancer Treat Rep 1984; 68: 221–32.PubMedGoogle Scholar
  53. 53.
    Oldham RK. Therapeutic monoclonal antibodies: effects of tumor cell heterogeniety. In: Present Status of Nontoxic Concepts in Cancer Therapy, Cancer Treatment Symposium ( Germany ), Karger, 1986.Google Scholar
  54. 54.
    Oldham RK, Foon KA, Morgan AC et al. Monoclonal antibody therapy of malignant melanoma: in vivo localization in cutaneous metastasis after intravenous administration. J Clin Oncol 1984; 2: 1235–42.PubMedGoogle Scholar
  55. 55.
    Oldham RK, Morgan AC, Woodhouse CS et al. Monoclonal antibodies in the treatment of cancer: preliminary observations and future prospects. Med Oncol Tumor Pharmocol 1984; 1: 51–62.Google Scholar
  56. 56.
    Oldham RK. Antibody-drug and antibody-toxin conjugates. In: Reif AE, Mitchell MS, eds. Immunity to Cancer. New York: Academic Press, 1985: 575–86.Google Scholar
  57. 57.
    Oldham RK. Monoclonal antibodies: does sufficient selectivity to cancer cells exist for therapeutic application? J Biol Response Modif 1987; 6: 227–34.Google Scholar
  58. 58.
    Oldham RK. Immunoconjugates: drugs and toxins. In: Oldham RK, ed. Principles of Cancer Biotherapy. New York: Raven Press, 1987: 319–35.Google Scholar
  59. 59.
    Oldham RK. Monoclonal antibody therapy. In: Chiao JW, ed. Biological Response Modifiers and Cancer Research, Vol. 40. New York: Marcel Dekker, 1988: 3–16.Google Scholar
  60. 60.
    Oldham RK, Lewis M, Orr DW et al. Individually specified drug immunoconjugates in cancer treatment. Imperial Cancer Research Conference, England, 1990.Google Scholar
  61. 61.
    Oldham RK. Who pays for new drugs? Nature 1988; 332: 795.PubMedCrossRefGoogle Scholar
  62. 62.
    Oldham RK, Lewis M, Orr DW et al. Adriamycin custom-tailored immunoconjugates in the treatment of human malignancies. Mol Biother 1988; 1: 103–13.PubMedGoogle Scholar
  63. 63.
    Oldham RK, Liao SK et al. Individually specified drug immunoconjugates in cancer treatment. In: Ceriani RL, ed. Breast Cancer Immunodiagnosis and Immunotherapy Proceedings, 1989: 219–30.CrossRefGoogle Scholar
  64. 64.
    Oldham RK. Monoclonal antibodies. In: Nathanson L, ed. Management of Advanced Melanoma. Contemporary Issues in Clinical Oncology. New York: Churchill Livingston, 1986: 195–207.Google Scholar
  65. 65.
    Oldham RK. Custom tailored drug immunoconjugates in cancer therapy. Mol Biother 1991; 3: 148–62.PubMedGoogle Scholar
  66. 66.
    Orr DW, Oldham RK, Lewis M et al. Phase I trial of mitomycin-c immunoconjugate cocktails in human malignancies. Mol Biother 1989; 1: 229–40.PubMedGoogle Scholar
  67. 67.
    Pavanasasivam G, Pearson JW, Bohn W et al. Immunotoxins to a human melanoma asociated antigen: comparison of gelonin with ricin and other A-chain conjugates. Cancer Res 1987; 47: 3169–73.Google Scholar
  68. 68.
    Philpott GW, Gass EH, Panker CW. Affinity cytotoxicity with an alcohol dehydrogenase-antibody conjugate and allyl alcohol. Cancer Res 1979; 39: 2084–7.PubMedGoogle Scholar
  69. 69.
    Pietersz GA, Smyth MJ, Kanellos J. Preclinical and clinical studies with a variety of immunoconjugates. Antibody Immunoconj Radiopharm 1988; 1: 79–103.Google Scholar
  70. 70.
    Raso V, Raso J, Basala M, Schlossman S. Monoclonal antibody-ricin A chain conjugate selectivity cytotoxic for cells bearing the common acute lymphoblastic leukemia antigen. Cancer Res 1980; 42: 457–64.Google Scholar
  71. 71.
    Riethmuller G, Holz E, Schlimok G et al. Monoclonal antibody therapy for resected Duke’s C colorectal cancer: seven-year outcome of a multicenter randomized trial. J Clin Oncol 1998, 16: 1788–94.PubMedGoogle Scholar
  72. 72.
    Ritz J, Schlossman SF. Utilization of monoclonal antibodies in treatment of leukemia and lymphoma. Blood 1982; 59: 1–11.PubMedGoogle Scholar
  73. 73.
    Rowland AJ, Pietersz GA. Reduction in the toxicity of aminopterin-monoclonal-antibody conjugates by leucovorin. Cancer Immunol Immunother 1994; 39: 135–9.PubMedGoogle Scholar
  74. 74.
    Rowland AJ, Pietersz GA, McKenzie IFC. Preclinical investigation of the antitumour effects of anti-CD19-idarubicin immunoconjugates. Cancer Immunol Immunother 1993; 37: 195–202.PubMedCrossRefGoogle Scholar
  75. 75.
    Rowland GF, Corvalan JRF, Axton CA et al. Suppression of growth of human colorectal tumor in nude mice by vindesine-monoclonal antibody CEA conjugates. Prot Biol Fluids 1984; 31: 783–6.Google Scholar
  76. 76.
    Rowland GF, Axton CA, Baldwin RW et al. Anitumor properties of vindesine-monoclonal antibody conjugates. Cancer Immunol Immunother 1985; 19: 1–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Rowland GF, Simmonds RG, Grove VA et al. Drug localization and growth inhibition studies of vindesinemonoclonal anti-CEA conjugates in human xenograft. Cancer Immunol Immunother, 1986; 21: 183–7.PubMedCrossRefGoogle Scholar
  78. 78.
    Schilsky RL. Tumor cell heterogeniety: implications for clinical practice. Semin Oncol 1985; 12: 203–6.PubMedGoogle Scholar
  79. 79.
    Schnipper LE. Clinical implications of tumor cell heterogeniety. N Engl Med 1986; 314: 1423–31.CrossRefGoogle Scholar
  80. 80.
    Schroff RW, Farrell MM, Klein RA et al. T65 antigen modulation in a phase I monoclonal antibody trial with chronic lymphocytic leukemia patients. J Immunol 1984; 133: 1641–8.PubMedGoogle Scholar
  81. 81.
    Schroff RW, Foon KA, Beatty SM et al. Human anti-murine immunoglobulin responses in patients receiving monoclonal antibody therapy. Cancer Res 1985; 45: 879–85.PubMedGoogle Scholar
  82. 82.
    Schroff RW, Morgan AC, Woodhouse CS et al. Monoclonal antibody therapy in malignant melanoma: factors effecting in vivo localization. J Biol Response Modif 1987; 6: 457–72.Google Scholar
  83. 83.
    Schroff RW, Woodhouse CS, Foon KA et al. Intratumor localization of monoclonal antibody in patients with melanoma treated with antibody to a 250Kd melanoma associated antigen. J Natl Cancer Inst 1985; 74: 299–306.PubMedGoogle Scholar
  84. 84.
    Sears HF, Herlym D, Steplewski Z, Koprowski H. Effects of monoclonal antibody immunotherapy in patients with gastrointestinal adenocarcinoma. J Biol Response Modif 1984; 3: 138–50.Google Scholar
  85. 85.
    Sears HF, Mattis J, Herlyn D et al. Phase-1 clinical trial of monoclonal antibody in treatment of gastrointestinal tumors. Lancet 1982; 1: 762–5.PubMedCrossRefGoogle Scholar
  86. 86.
    Shawler DL, Johnson DE, Sweet MD et al. Preclinical trials using an immunoconjugate of T101 and methotrexate in an athymic mouse/human T-cell tumor model. J Biol Response Modif 1988; 7: 608–18.Google Scholar
  87. 87.
    Sievers EL, Larson RA, Stadtmauer EA, Appelbaum FR et al. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol 2001; 19: 3244–54.PubMedGoogle Scholar
  88. 88.
    Sivam G, Comezoglu FT, Vrudhula VM et al. Immunoconjugates of a small molecule protein synthesis inhibitor (trichothecene) - an update. Antibody Immunoconj Radiopharm 1990; 3: 63.Google Scholar
  89. 89.
    Sjogren HO, Isaksson M, Willner D et al. Antitumor activity of carcinoma-reactive BR96-doxorubicin conjugate against human carcinomas in athymic mice and rats and syngeneic rat carcinomas in immunocompetent rats. Cancer Res 1997; 57: 4530–6.PubMedGoogle Scholar
  90. 90.
    Smith TW. Antitumor properties of vindesine-monoclonal antibody conjugates. Cancer Immunol Immunother 1985; 19: 1–7.Google Scholar
  91. 91.
    Stastny JJ, Das Gupta TK. The use of daunomycin-antibody immunoconjugates in managing soft tissue sarcomas: nude mouse xenograft model. Cancer Res 1993; 53: 5740–4.PubMedGoogle Scholar
  92. 92.
    Takahashi T, Yamaguchi T, Noguchi A et al. Clinical trial of monoclonal antibody-drug conjugate, A7-NCS, for 70 patients with colorectal cancer. Antibody Immunoconj Radiopharm 1990; 3: 60.Google Scholar
  93. 93.
    Thorpe PE, Ross WCJ. The preparation and cytotoxic properties of antibody-toxin conjugates. Immunol Rev 1982; 62: 119.PubMedCrossRefGoogle Scholar
  94. 94.
    Toshiyuki S, Nagamura S, Saito H et al. Synthesis of a novel duocarmycin derivative DU-257 and its application to immunoconjugate using poly(ethylene glycol)-dipeptidyl linker capable of tumor specific activation. Bioorg Med Chem 2000; 8: 2175–84.CrossRefGoogle Scholar
  95. 95.
    Trail PA, Willner D, Lasch SJ et al. Cure of xenografted human carcinomas by BR960-doxorubicin immunoconjugates. Science 1993; 261: 212–15.PubMedCrossRefGoogle Scholar
  96. 96.
    Trail PA, Willner D, Hellstrom KE. Site-directed delivery of anthracyclines for cancer therapy. Drug Dev Res 1995; 34: 196–209.CrossRefGoogle Scholar
  97. 97.
    Tsukada Y, Hurwitz E, Kashi R et al. Chemotherapy by intravenous administration of conjugates of daunomycin with monoclonal conventional anti -rat-alpha-fetoprotein antibodies. Proc Natl Acad Sci USA 1982; 79: 7896–9.PubMedCrossRefGoogle Scholar
  98. 98.
    Uckun FM, Evans WE, Forsyth CJ et al. Biotherapy of B-cell precursor leukemia by targeting genistein to CD19- associated tyrosine kinases. Science 267: 886–91.Google Scholar
  99. 99.
    van der Velden VHJ, te Marvelde JG, Hoogeveen PG et al. Targeting of the CD33–calicheamicin immunoconjugate Mylotarg (CMA–676) in acute myeloid leukemia: in vivo and in vitro saturation and internalization by leukemic and normal myeloid cells. Blood 2001; 97: 3197–2–04.Google Scholar
  100. 100.
    Vogel C, Cobleigh MA, Tripathy D et al. First-line, single-agent Herceptin (trastuzumab) in metastatic breast cancer: a preliminary report. Eur J Cancer 2001; 37 (Suppl. 1): S 25–9.PubMedCrossRefGoogle Scholar
  101. 101.
    Vogel C-W, ed. Immunoconjugates: Antibody Conjugates in Radioimaging and Therapy of Cancer. New York; Oxford University Press, 1987.Google Scholar
  102. 102.
    Von Hoff DD. Implications of tumor cell heterogeneity for in vitro drug sensitivity testing. Semin Oncol 1985; 12: 327–31.Google Scholar
  103. 103.
    Yarbro JW. Introduction: tumor heterogeniety and the new biology. Semin Oncol 1985; 12: 201–2.Google Scholar
  104. 104.
    Yoshibumi K, Tsukazaki K, Kubushiro K et al. Selective cytotoxicity of adriamycin immunoconjugate antibody MSN-1 to endometrial adenocarcinoma in vitro and in vivo. Oncol Rep 2000; 7: 1099–106.Google Scholar
  105. 105.
    Second conference on radioimmunodetection and radioimmunotherapy of cancer. Cancer Res Suppl 1990; 50: 773s - 1059s.Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2003

Authors and Affiliations

  • Malek Safa
  • Kenneth A. Foon
  • Robert K. Oldham

There are no affiliations available

Personalised recommendations