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. 1994 Oct;70(4):753–758. doi: 10.1038/bjc.1994.390

m17-1A-, c17-1A- and cSF25-mediated antibody-dependent cell-mediated cytotoxicity in patients with advanced cancer.

A M Pullyblank 1, P J Guillou 1, J R Monson 1
PMCID: PMC2033396  PMID: 7917934

Abstract

The anti-tumour antibody-dependent cell-mediated cytotoxicity (ADCC) capacity of the conventional antibody m17-1A was compared with its chimerised analogue c17-1A and a newer chimeric antibody, cSF25, specific for colonic adenocarcinoma. The results (AUC units +/- s.e.m., control versus cancer) show that mononuclear cells from patients with adenocarcinoma mediate ADCC as efficiently as those from controls for m17-1A (143 +/- 14 vs 153 +/- 14), c17-1A (174 +/- 16 vs 189 +/- 14) cSF25 (215 +/- 18 vs 237 +/- 13) and effectors and targets alone (57 +/- 9 vs 51 +/- 8). Both chimeric antibodies mediated ADCC more effectively than m17-1A with cSF25 consistently producing the highest lysis. Furthermore, more efficient ADCC was found to correspond with monocyte activation examined flow cytometrically. The results (mean channel fluorescence) show that HLA-DR expression is increased with c17-1A (1436 +/- 200) and cSF25 (2252 +/- 298) above that observed when effectors and targets were incubated alone (1157 +/- 168) or with m17-1A (1286 +/- 170). Similarly, interleukin 2 receptor (IL-2R) expression (percentage of positive cells) was augmented in the presence of m17-1A (15 +/- 3), c17-1A (14 +/- 3) and cSF25 (25 +/- 3) when compared with no antibody (9 +/- 2). We discuss the possibility that the superior ADCC activity of chimeric antibodies, especially cSF25, may be due to increased monocyte activation.

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Selected References

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  1. Adams D. O., Hall T., Steplewski Z., Koprowski H. Tumors undergoing rejection induced by monoclonal antibodies of the IgG2a isotype contain increased numbers of macrophages activated for a distinctive form of antibody-dependent cytolysis. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3506–3510. doi: 10.1073/pnas.81.11.3506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buchsbaum D. J., Brubaker P. G., Hanna D. E., Glatfelter A. A., Terry V. H., Guilbault D. M., Steplewski Z. Comparative binding and preclinical localization and therapy studies with radiolabeled human chimeric and murine 17-1A monoclonal antibodies. Cancer Res. 1990 Feb 1;50(3 Suppl):993s–999s. [PubMed] [Google Scholar]
  3. Dye J. F., Somers S. S., Guillou P. J. Simplified quantitation of cytotoxicity by integration of specific lysis against effector cell concentration at a constant target cell concentration and measuring the area under the curve. J Immunol Methods. 1991 Apr 8;138(1):1–13. doi: 10.1016/0022-1759(91)90058-n. [DOI] [PubMed] [Google Scholar]
  4. Graziano R. F., Fanger M. W. Fc gamma RI and Fc gamma RII on monocytes and granulocytes are cytotoxic trigger molecules for tumor cells. J Immunol. 1987 Nov 15;139(10):3536–3541. [PubMed] [Google Scholar]
  5. Göttlinger H. G., Funke I., Johnson J. P., Gokel J. M., Riethmüller 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 Jul 15;38(1):47–53. doi: 10.1002/ijc.2910380109. [DOI] [PubMed] [Google Scholar]
  6. Hellström I., Garrigues U., Lavie E., Hellström K. E. Antibody-mediated killing of human tumor cells by attached effector cells. Cancer Res. 1988 Feb 1;48(3):624–627. [PubMed] [Google Scholar]
  7. Herlyn D., Herlyn M., Steplewski Z., Koprowski H. Monoclonal antibodies in cell-mediated cytotoxicity against human melanoma and colorectal carcinoma. Eur J Immunol. 1979 Aug;9(8):657–659. doi: 10.1002/eji.1830090817. [DOI] [PubMed] [Google Scholar]
  8. Herlyn D., Koprowski H. IgG2a monoclonal antibodies inhibit human tumor growth through interaction with effector cells. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4761–4765. doi: 10.1073/pnas.79.15.4761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hersh E. V., Murphy S. G., Gutterman J. U., Morgan J., Quesada J., Zander A., Stewart D. Antibody-dependent cell-mediated cytotoxicity in human cancer: characterization of patient leukocyte activity and treatment effects. Cancer. 1982 Jan 15;49(2):251–260. doi: 10.1002/1097-0142(19820115)49:2<251::aid-cncr2820490210>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  10. Johnson W. J., Steplewski Z., Matthews T. J., Hamilton T. A., Koprowski H., Adams D. O. Cytolytic interactions between murine macrophages, tumor cells, and monoclonal antibodies: characterization of lytic conditions and requirements for effector activation. J Immunol. 1986 Jun 15;136(12):4704–4713. [PubMed] [Google Scholar]
  11. Khazaeli M. B., Saleh M. N., Wheeler R. H., Huster W. J., Holden H., Carrano R., LoBuglio A. F. Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A. II. Pharmacokinetics and immune response. J Natl Cancer Inst. 1988 Aug 17;80(12):937–942. doi: 10.1093/jnci/80.12.937. [DOI] [PubMed] [Google Scholar]
  12. Liu A. Y., Robinson R. R., Hellström K. E., Murray E. D., Jr, Chang C. P., Hellström I. Chimeric mouse-human IgG1 antibody that can mediate lysis of cancer cells. Proc Natl Acad Sci U S A. 1987 May;84(10):3439–3443. doi: 10.1073/pnas.84.10.3439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Liu A. Y., Robinson R. R., Murray E. D., Jr, Ledbetter J. A., Hellström I., Hellström K. E. Production of a mouse-human chimeric monoclonal antibody to CD20 with potent Fc-dependent biologic activity. J Immunol. 1987 Nov 15;139(10):3521–3526. [PubMed] [Google Scholar]
  14. LoBuglio A. F., Wheeler R. H., Trang J., Haynes A., Rogers K., Harvey E. B., Sun L., Ghrayeb J., Khazaeli M. B. Mouse/human chimeric monoclonal antibody in man: kinetics and immune response. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4220–4224. doi: 10.1073/pnas.86.11.4220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lubeck M. D., Steplewski Z., Baglia F., Klein M. H., Dorrington K. J., Koprowski H. The interaction of murine IgG subclass proteins with human monocyte Fc receptors. J Immunol. 1985 Aug;135(2):1299–1304. [PubMed] [Google Scholar]
  16. Masucci G., Lindemalm C., Frödin J. E., Hagström B., Mellstedt H. Effect of human blood mononuclear cell populations in antibody dependent cellular cytotoxicity (ADCC) using two murine (CO17-1A and Br55-2) and one chimeric (17-1A) monoclonal antibodies against a human colorectal carcinoma cell line (SW948). Hybridoma. 1988 Oct;7(5):429–440. doi: 10.1089/hyb.1988.7.429. [DOI] [PubMed] [Google Scholar]
  17. McCarley D. L., Shah V. O., Weiner R. S. Purified human monocyte subsets as effector cells in antibody-dependent cellular cytotoxicity (ADCC). J Immunol. 1983 Oct;131(4):1780–1783. [PubMed] [Google Scholar]
  18. McCredie J. A., MacDonald H. R., Wood S. B. Effect of operation and radiotherapy on antibody-dependent cellular cytotoxicity. Cancer. 1979 Jul;44(1):99–105. doi: 10.1002/1097-0142(197907)44:1<99::aid-cncr2820440118>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  19. Morrison S. L., Johnson M. J., Herzenberg L. A., Oi V. T. Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6851–6855. doi: 10.1073/pnas.81.21.6851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nishimura Y., Yokoyama M., Araki K., Ueda R., Kudo A., Watanabe T. Recombinant human-mouse chimeric monoclonal antibody specific for common acute lymphocytic leukemia antigen. Cancer Res. 1987 Feb 15;47(4):999–1005. [PubMed] [Google Scholar]
  21. Ortaldo J. R., Woodhouse C., Morgan A. C., Herberman R. B., Cheresh D. A., Reisfeld R. Analysis of effector cells in human antibody-dependent cellular cytotoxicity with murine monoclonal antibodies. J Immunol. 1987 May 15;138(10):3566–3572. [PubMed] [Google Scholar]
  22. Pimm M. V., Perkins A. C., Armitage N. C., Baldwin R. W. The characteristics of blood-borne radiolabels and the effect of anti-mouse IgG antibodies on localization of radiolabeled monoclonal antibody in cancer patients. J Nucl Med. 1985 Sep;26(9):1011–1023. [PubMed] [Google Scholar]
  23. Sears H. F., Atkinson B., Mattis J., Ernst C., Herlyn D., Steplewski Z., Häyry P., Koprowski H. Phase-I clinical trial of monoclonal antibody in treatment of gastrointestinal tumours. Lancet. 1982 Apr 3;1(8275):762–765. doi: 10.1016/s0140-6736(82)91811-6. [DOI] [PubMed] [Google Scholar]
  24. Shaw D. R., Khazaeli M. B., LoBuglio A. F. Mouse/human chimeric antibodies to a tumor-associated antigen: biologic activity of the four human IgG subclasses. J Natl Cancer Inst. 1988 Dec 7;80(19):1553–1559. doi: 10.1093/jnci/80.19.1553. [DOI] [PubMed] [Google Scholar]
  25. Shaw D. R., Khazaeli M. B., Sun L. K., Ghrayeb J., Daddona P. E., McKinney S., LoBuglio A. F. Characterization of a mouse/human chimeric monoclonal antibody (17-1A) to a colon cancer tumor-associated antigen. J Immunol. 1987 Jun 15;138(12):4534–4538. [PubMed] [Google Scholar]
  26. Steplewski Z., Herlyn D., Lubeck M., Kimoto Y., Herlyn M., Koprowski H. Mechanisms of tumor growth inhibition. Hybridoma. 1986 Jul;5 (Suppl 1):S59–S64. [PubMed] [Google Scholar]
  27. Steplewski Z., Lubeck M. D., Koprowski H. Human macrophages armed with murine immunoglobulin G2a antibodies to tumors destroy human cancer cells. Science. 1983 Aug 26;221(4613):865–867. doi: 10.1126/science.6879183. [DOI] [PubMed] [Google Scholar]
  28. Steplewski Z., Sun L. K., Shearman C. W., Ghrayeb J., Daddona P., Koprowski H. Biological activity of human-mouse IgG1, IgG2, IgG3, and IgG4 chimeric monoclonal antibodies with antitumor specificity. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4852–4856. doi: 10.1073/pnas.85.13.4852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Stratton M. L., Herz J., Loeffler R. A., McClurg F. L., Reiter A., Bernstein P., Danley D. L., Benjamini E. Antibody-dependent cell-mediated cytotoxicity in treated and nontreated cancer patients. Cancer. 1977 Sep;40(3):1045–1051. doi: 10.1002/1097-0142(197709)40:3<1045::aid-cncr2820400312>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  30. Sun L. K., Curtis P., Rakowicz-Szulczynska E., Ghrayeb J., Chang N., Morrison S. L., Koprowski H. Chimeric antibody with human constant regions and mouse variable regions directed against carcinoma-associated antigen 17-1A. Proc Natl Acad Sci U S A. 1987 Jan;84(1):214–218. doi: 10.1073/pnas.84.1.214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Takahashi H., Carlson R., Ozturk M., Sun S., Motte P., Strauss W., Isselbacher K. J., Wands J. R., Shouval D. Radioimmunolocation of hepatic and pulmonary metastasis of human colon adenocarcinoma. Gastroenterology. 1989 May;96(5 Pt 1):1317–1329. doi: 10.1016/s0016-5085(89)80019-8. [DOI] [PubMed] [Google Scholar]
  32. Takahashi H., Wilson B., Ozturk M., Motté P., Strauss W., Isselbacher K. J., Wands J. R. In vivo localization of human colon adenocarcinoma by monoclonal antibody binding to a highly expressed cell surface antigen. Cancer Res. 1988 Nov 15;48(22):6573–6579. [PubMed] [Google Scholar]

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