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. 1991 May;33(3):153–157. doi: 10.1007/BF01756135

Biological activity in the human system of isotype variants of oligosaccharide-Y-specific murine monoclonal antibodies

Dieter Scholz 1, Michael Lubeck 2, Hans Loibner 1, Joan McDonald-Smith 2, Yasuhiko Kimoto 2, Hilary Koprowski 2, Zeoon Steplewski 2,✉
PMCID: PMC11038553  PMID: 2044080

Abstract

The capacity of isotype variants of BR55-2, an anti-tumor monoclonal antibody directed against Y oligosaccharide, to mediate antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in the human system was evaluated using freshly isolated peripheral blood mononuclear cells, lymphocytes, monocytes and complement. The ADCC activities of the BR55-2 IgG3 isotype and its switch variants (IgG1, IgG2b, and IgG2a) with human monocytes were high for all isotypes, whereas the activity of all isotypes was lower with freshly isolated lymphocytes, IgG1 being the least effective. The CDC on the other hand was strong with IgG3, IgG2b and IgG2a and negative with the IgG1 variant. The IgG3 and IgG2a isotypes were selected for further development. Their strong ADCC and CDC activity against mammary carcinoma, colon carcinoma and small-cell lung tumor cell lines was confirmed quantitatively using proteins highly purified from tissue-culture supernatants. Significant variations in ADCC and CDC competence was observed among human donors.

Key words: Y oligosaccharide antigen, mAb isotype variants, Human effector mechanisms

Footnotes

This work was supported by grants CA 10 815, CA 25 874 and CA 21124 from the National Institutes of Health

References

  • 1.Barth A, Waibel R, Stahel RA (1991) Monoclonal anti-idiotypic antibody mimicking a tumor-associated sialoglycoprotein antigen induces humoral immune response against human small cell lung carcinoma (in press) [DOI] [PubMed]
  • 2.Boyum A. Isolation of leucocytes from human blood. A twophase system for removal of red cells with methylcellulose as erythrocyte-aggregating agent. Scand J Clin Lab Invest. 1968;21(Suppl.):9. [PubMed] [Google Scholar]
  • 3.Brown SL, Miller RA, Horning SJ, Czerwinski D, Hart SM, McElderry R, Basham T, Warnke RA, Merigan TC, Levy R. Treatment of B-cell lymphomas with anti-idiotype antibodies alone and in combination with alpha interferon. Blood. 1989;73:651. [PubMed] [Google Scholar]
  • 4.Freundlich B, Avdalovic NJ. Use of gelatin/plasma coated flasks for isolating human peripheral blood monocytes. Immunol Methods. 1983;62:31. doi: 10.1016/0022-1759(83)90107-2. [DOI] [PubMed] [Google Scholar]
  • 5.Frodin J, Harmenberg U, Biberfeld P, Christensson B, Lefvert A, Rieger A, Shetye J, Wahren B, Mellstedt H. Clinical effects of monoclonal antibodies (MAb 17-1A) in patients with metastatic colorectal carcinomas. Hybridoma. 1988;7:309. doi: 10.1089/hyb.1988.7.309. [DOI] [PubMed] [Google Scholar]
  • 6.Haisma HJ, Battaile S, Stradtmon EW, Knapp RC, Zurawski NR. Antibody-antigen complex formation following injection of OC125 monoclonal antibody in patients with ovarian cancer. Int J Cancer. 1987;40:758. doi: 10.1002/ijc.2910400608. [DOI] [PubMed] [Google Scholar]
  • 7.Herlyn D, Herlyn M, Steplewski Z, Koprowski H. Monoclonal anti-human tumor antibodies of six isotypes in cytotoxic reactions with human and murine effector cells. Cell Immunol. 1985;92:105. doi: 10.1016/0008-8749(85)90068-1. [DOI] [PubMed] [Google Scholar]
  • 8.Herlyn I, Koprowski H. IgG2 monoclonal antibodies inhibit human tumor growth through interaction with effector cells. Proc Natl Acad Sci (USA) 1982;79:4761. doi: 10.1073/pnas.79.15.4761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Houghton AN, Mintzer D, Cordon-Cardo C, Welt S, Fliegel B, Vadhan S, Carswell E., Melamed MR, Oettgen HF, Old LJ. Mouse monoclonal IgG3 antibody detecting GD3 ganglioside: a phase I trial in patients with malignant melanoma. Proc Natl. Acad Sci USA. 1985;82:1242. doi: 10.1073/pnas.82.4.1242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Johnson NJ, Adams DO. Assays detecting the antibody-dependent and independent binding and cytolysis of tumor cells by murine macrophages. Methods Enzymol. 1986;132:555. doi: 10.1016/s0076-6879(86)32041-x. [DOI] [PubMed] [Google Scholar]
  • 11.Koprowski H, Steplewski Z, Mitchell KF, Herlyn M, Herlyn D, Fuhrer KP. Colorectal carcinoma antigens detected by hybridoma antibodies. Somat Cell Genet. 1979;5:957. doi: 10.1007/BF01542654. [DOI] [PubMed] [Google Scholar]
  • 12.Lowder JN, Meeker CT, Campbell M, Garcia FC, Gralow J, Miller RA, Warnke R, Levy R. Studies on B lymphoid tumors treated with monoclonal anti-idiotype antibodies: correlation with clinical response. Blood. 1982;69:199. [PubMed] [Google Scholar]
  • 13.Lubeck MD, Steplewski Z, Baglia F, Klein MH, Dorrington K, Koprowski H. The interaction of murine IgG subclass proteins with human monocyte Fc receptors. Immunology. 1985;135:1299. [PubMed] [Google Scholar]
  • 14.Lubeck MD, Kimoto Y, Steplewski Z, Koprowski H. Killing of human tumor cell lines by human monocytes and murine monoclonal antibodies. Cell Immunol. 1988;111:107. doi: 10.1016/0008-8749(88)90055-x. [DOI] [PubMed] [Google Scholar]
  • 15.Scholz D, Bednarik K, Neruda W. Mediation of tumor cell lysis by murine monoclonal antibodies. The lysis efficacy of whole human blood in comparison to PBMCs and complement. Cancer Detect Prev. 1989;14:118. [Google Scholar]
  • 16.Sears HF, Atkinson B, Mattis J, Ernst C, Herlyn D, Steplewski Z, Hayry P, Koprowski H. Phase I clinical trial of monoclonal antibody treatment of gastrointestinal tumors. Lancet. 1982;1:762. doi: 10.1016/s0140-6736(82)91811-6. [DOI] [PubMed] [Google Scholar]
  • 17.Sears HF, Herlyn D, Steplewski Z, Koprowski H. Effects of monoclonal antibody immunotherapy on patients with gastrointestinal adenocarcinoma. J Biol Response Mod. 1984;3:138. [PubMed] [Google Scholar]
  • 18.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. [PubMed] [Google Scholar]
  • 19.Soule HD, Vazquez J, Long A, Albert S, Brennan M. A human cell line from a pleural effusion derived from a breast carcinoma. Natl Cancer Inst. 1973;51:1409. doi: 10.1093/jnci/51.5.1409. [DOI] [PubMed] [Google Scholar]
  • 20.Steplewski Z, Blaszczyk M, Herlyn D, Herlyn M, Koprowski H. Effector cells in ADCC with anti-breast cancer monoclonal antibodies. In: Ceriani, editor. Monoclonal antibodies and breast cancer. San Francisco: Nijhoff; 1985. pp. 134–149. [Google Scholar]
  • 21.Steplewski Z, Blaszczyk-Thurin M, Lubeck MD, Loibner H, Scholz D, Koprowski H. Oligosaccharide Y specific monoclonal antibody and its isotype switch variants. Hybridoma. 1990;9:201. doi: 10.1089/hyb.1990.9.201. [DOI] [PubMed] [Google Scholar]
  • 22.Steplewski Z, Lubeck MD, Scholz D, Loibner H, McDonald-Smith J, Koprowski H (1991) Tumor cell lysis and tumor growth inhibition by the isotype switch variants of MAb BR55-2 directed against Y6 blood group related epitope. In vivo (in press) [PubMed]
  • 23.Wiltrout RH, Toramelli D, Holden HT. Indium-111 assay of macrophage-mediated cytolysis. In: Hersco HB, Holden HT, Bellanti JA, Graffar A, editors. Manual of macrophage methodology. New York: Dekker; 1981. pp. 337–344. [Google Scholar]

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