Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Apr 15;88(8):3305–3309. doi: 10.1073/pnas.88.8.3305

Use of heteropolymeric monoclonal antibodies to attach antigens to the C3b receptor of human erythrocytes: a potential therapeutic treatment.

R P Taylor 1, W M Sutherland 1, C J Reist 1, D J Webb 1, E L Wright 1, R H Labuguen 1
PMCID: PMC51435  PMID: 1826564

Abstract

We have prepared bispecific, cross-linked monoclonal antibodies (heteropolymers) with specificity for both targeted antigens and the human erythrocyte (RBC) complement receptor. These heteropolymers facilitate binding of target antigens (human IgG and dinitrophenylated bovine gamma globulin) to human RBCs under conditions that either allow or preclude complement activation. Quantitative analyses of this binding agree well with the number of complement receptors per RBC. In vitro "whole-blood" model experiments indicate heteropolymer-facilitated binding of antigens to RBCs is rapid and stable at 37 degrees C. It may be possible to extend these prototype experiments to the in vivo situation and use heteropolymer-attached RBCs for the safe and rapid binding, neutralization, and removal from the circulation of pathogenic antigens associated with infectious disease.

Full text

PDF
3305

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahearn J. M., Fearon D. T. Structure and function of the complement receptors, CR1 (CD35) and CR2 (CD21). Adv Immunol. 1989;46:183–219. doi: 10.1016/s0065-2776(08)60654-9. [DOI] [PubMed] [Google Scholar]
  2. Atkinson J. P. Complement activation and complement receptors in systemic lupus erythematosus. Springer Semin Immunopathol. 1986;9(2-3):179–194. doi: 10.1007/BF02099021. [DOI] [PubMed] [Google Scholar]
  3. Chevalier J., Kazatchkine M. D. Distribution in clusters of complement receptor type one (CR1) on human erythrocytes. J Immunol. 1989 Mar 15;142(6):2031–2036. [PubMed] [Google Scholar]
  4. Coombs R. W., Collier A. C., Allain J. P., Nikora B., Leuther M., Gjerset G. F., Corey L. Plasma viremia in human immunodeficiency virus infection. N Engl J Med. 1989 Dec 14;321(24):1626–1631. doi: 10.1056/NEJM198912143212402. [DOI] [PubMed] [Google Scholar]
  5. Cornacoff J. B., Hebert L. A., Smead W. L., VanAman M. E., Birmingham D. J., Waxman F. J. Primate erythrocyte-immune complex-clearing mechanism. J Clin Invest. 1983 Feb;71(2):236–247. doi: 10.1172/JCI110764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Courtenay-Luck N. S., Epenetos A. A., Moore R., Larche M., Pectasides D., Dhokia B., Ritter M. A. Development of primary and secondary immune responses to mouse monoclonal antibodies used in the diagnosis and therapy of malignant neoplasms. Cancer Res. 1986 Dec;46(12 Pt 1):6489–6493. [PubMed] [Google Scholar]
  7. Edberg J. C., Kujala G. A., Taylor R. P. Rapid immune adherence reactivity of nascent, soluble antibody/DNA immune complexes in the circulation. J Immunol. 1987 Aug 15;139(4):1240–1244. [PubMed] [Google Scholar]
  8. Edberg J. C., Tosic L., Wright E. L., Sutherland W. M., Taylor R. P. Quantitative analyses of the relationship between C3 consumption, C3b capture, and immune adherence of complement-fixing antibody/DNA immune complexes. J Immunol. 1988 Dec 15;141(12):4258–4265. [PubMed] [Google Scholar]
  9. Edberg J. C., Wright E., Taylor R. P. Quantitative analyses of the binding of soluble complement-fixing antibody/dsDNA immune complexes to CR1 on human red blood cells. J Immunol. 1987 Dec 1;139(11):3739–3747. [PubMed] [Google Scholar]
  10. Emlen W., Burdick G., Carl V., Lachmann P. J. Binding of model immune complexes to erythrocyte CR1 facilitates immune complex uptake by U937 cells. J Immunol. 1989 Jun 15;142(12):4366–4371. [PubMed] [Google Scholar]
  11. Fearon D. T. Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, B lymphocyte, and monocyte. J Exp Med. 1980 Jul 1;152(1):20–30. doi: 10.1084/jem.152.1.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
  13. Hebert L. A., Cosio G. The erythrocyte-immune complex-glomerulonephritis connection in man. Kidney Int. 1987 Apr;31(4):877–885. doi: 10.1038/ki.1987.81. [DOI] [PubMed] [Google Scholar]
  14. Ho D. D., Moudgil T., Alam M. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N Engl J Med. 1989 Dec 14;321(24):1621–1625. doi: 10.1056/NEJM198912143212401. [DOI] [PubMed] [Google Scholar]
  15. Horgan C., Burge J., Crawford L., Taylor R. P. The kinetics of [3H]-dsDNA/anti-DNA immune complex formation, binding by red blood cells, and release into serum: effect of DNA molecular weight and conditions of antibody excess. J Immunol. 1984 Oct;133(4):2079–2084. [PubMed] [Google Scholar]
  16. Hourcade D., Holers V. M., Atkinson J. P. The regulators of complement activation (RCA) gene cluster. Adv Immunol. 1989;45:381–416. doi: 10.1016/s0065-2776(08)60697-5. [DOI] [PubMed] [Google Scholar]
  17. Karpovsky B., Titus J. A., Stephany D. A., Segal D. M. Production of target-specific effector cells using hetero-cross-linked aggregates containing anti-target cell and anti-Fc gamma receptor antibodies. J Exp Med. 1984 Dec 1;160(6):1686–1701. doi: 10.1084/jem.160.6.1686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Kimberly R. P., Edberg J. C., Merriam L. T., Clarkson S. B., Unkeless J. C., Taylor R. P. In vivo handling of soluble complement fixing Ab/dsDNA immune complexes in chimpanzees. J Clin Invest. 1989 Sep;84(3):962–970. doi: 10.1172/JCI114259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Livingston D. M. Immunoaffinity chromatography of proteins. Methods Enzymol. 1974;34:723–731. doi: 10.1016/s0076-6879(74)34094-3. [DOI] [PubMed] [Google Scholar]
  21. Medof M. E., Iida K., Mold C., Nussenzweig V. Unique role of the complement receptor CR1 in the degradation of C3b associated with immune complexes. J Exp Med. 1982 Dec 1;156(6):1739–1754. doi: 10.1084/jem.156.6.1739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Miyakawa Y., Yamada A., Kosaka K., Tsuda F., Kosugi E., Mayumi M. Defective immune-adherence (C3b) receptor on erythrocytes from patients with systemic lupus erythematosus. Lancet. 1981 Sep 5;2(8245):493–497. doi: 10.1016/s0140-6736(81)90882-5. [DOI] [PubMed] [Google Scholar]
  23. Mueller B. M., Reisfeld R. A., Gillies S. D. Serum half-life and tumor localization of a chimeric antibody deleted of the CH2 domain and directed against the disialoganglioside GD2. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5702–5705. doi: 10.1073/pnas.87.15.5702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. NELSON R. A., Jr The immune-adherence phenomenon; a hypothetical role of erythrocytes in defence against bacteria and viruses. Proc R Soc Med. 1956 Jan;49(1):55–58. [PMC free article] [PubMed] [Google Scholar]
  25. NELSON R. A., Jr The immune-adherence phenomenon; an immunologically specific reaction between microorganisms and erythrocytes leading to enhanced phagocytosis. Science. 1953 Dec 18;118(3077):733–737. doi: 10.1126/science.118.3077.733. [DOI] [PubMed] [Google Scholar]
  26. O'Shea J. J., Brown E. J., Seligmann B. E., Metcalf J. A., Frank M. M., Gallin J. I. Evidence for distinct intracellular pools of receptors for C3b and C3bi in human neutrophils. J Immunol. 1985 Apr;134(4):2580–2587. [PubMed] [Google Scholar]
  27. Paccaud J. P., Carpentier J. L., Schifferli J. A. Direct evidence for the clustered nature of complement receptors type 1 on the erythrocyte membrane. J Immunol. 1988 Dec 1;141(11):3889–3894. [PubMed] [Google Scholar]
  28. Perez P., Hoffman R. W., Shaw S., Bluestone J. A., Segal D. M. Specific targeting of cytotoxic T cells by anti-T3 linked to anti-target cell antibody. Nature. 1985 Jul 25;316(6026):354–356. doi: 10.1038/316354a0. [DOI] [PubMed] [Google Scholar]
  29. Ross G. D., Medof M. E. Membrane complement receptors specific for bound fragments of C3. Adv Immunol. 1985;37:217–267. doi: 10.1016/s0065-2776(08)60341-7. [DOI] [PubMed] [Google Scholar]
  30. Ross G. D., Yount W. J., Walport M. J., Winfield J. B., Parker C. J., Fuller C. R., Taylor R. P., Myones B. L., Lachmann P. J. Disease-associated loss of erythrocyte complement receptors (CR1, C3b receptors) in patients with systemic lupus erythematosus and other diseases involving autoantibodies and/or complement activation. J Immunol. 1985 Sep;135(3):2005–2014. [PubMed] [Google Scholar]
  31. Schifferli J. A., Ng Y. C., Estreicher J., Walport M. J. The clearance of tetanus toxoid/anti-tetanus toxoid immune complexes from the circulation of humans. Complement- and erythrocyte complement receptor 1-dependent mechanisms. J Immunol. 1988 Feb 1;140(3):899–904. [PubMed] [Google Scholar]
  32. Schifferli J. A., Taylor R. P. Physiological and pathological aspects of circulating immune complexes. Kidney Int. 1989 Apr;35(4):993–1003. doi: 10.1038/ki.1989.83. [DOI] [PubMed] [Google Scholar]
  33. Schroff R. W., Foon K. A., Beatty S. M., Oldham R. K., Morgan A. C., Jr Human anti-murine immunoglobulin responses in patients receiving monoclonal antibody therapy. Cancer Res. 1985 Feb;45(2):879–885. [PubMed] [Google Scholar]
  34. Shen L., Guyre P. M., Anderson C. L., Fanger M. W. Heteroantibody-mediated cytotoxicity: antibody to the high affinity Fc receptor for IgG mediates cytotoxicity by human monocytes that is enhanced by interferon-gamma and is not blocked by human IgG. J Immunol. 1986 Dec 1;137(11):3378–3382. [PubMed] [Google Scholar]
  35. Staerz U. D., Kanagawa O., Bevan M. J. Hybrid antibodies can target sites for attack by T cells. Nature. 1985 Apr 18;314(6012):628–631. doi: 10.1038/314628a0. [DOI] [PubMed] [Google Scholar]
  36. Tausk F. A., McCutchan A., Spechko P., Schreiber R. D., Gigli I. Altered erythrocyte C3b receptor expression, immune complexes, and complement activation in homosexual men in varying risk groups for acquired immune deficiency syndrome. J Clin Invest. 1986 Oct;78(4):977–982. doi: 10.1172/JCI112688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Taylor R. P., Wright E. L., Pocanic F. Quantitative analyses of C3b capture and immune adherence of IgM antibody/dsDNA immune complexes. J Immunol. 1989 Dec 1;143(11):3626–3631. [PubMed] [Google Scholar]
  38. Titus J. A., Perez P., Kaubisch A., Garrido M. A., Segal D. M. Human K/natural killer cells targeted with hetero-cross-linked antibodies specifically lyse tumor cells in vitro and prevent tumor growth in vivo. J Immunol. 1987 Nov 1;139(9):3153–3158. [PubMed] [Google Scholar]
  39. Tyler D. S., Stanley S. D., Zolla-Pazner S., Gorny M. K., Shadduck P. P., Langlois A. J., Matthews T. J., Bolognesi D. P., Palker T. J., Weinhold K. J. Identification of sites within gp41 that serve as targets for antibody-dependent cellular cytotoxicity by using human monoclonal antibodies. J Immunol. 1990 Nov 15;145(10):3276–3282. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES