Abstract
The immune system has long been recognised as playing a central role in the organism's defence against infectious diseases and possibly the development of neoplasia. The active stimulation of the immune system by immunisation and the passive administration of antitoxins have a venerable history in medicine. Yet the concept that antibodies may be used to modify physiological or pharmacological effects or may act as diagnostic agents in the living organisms has only recently come to be recognised. Advances, both in an understanding of the structural chemistry of the antibody molecule and in the ability to culture antibody-producing cells, now permit the selection and production of homogeneous antibodies and their smaller fragments in quantity by means other than conventional immunisation. These innovations will allow the development of a new pharmacology based on the remarkable resolving power of the antibody combining site. Antibodies or their fragments are shown to inhibit the pressor action of renin, to neutralise the pharmacological actions of digitalis, to block the beta-adrenergic receptor, and to detect and image myocardial infarcts.
Full text
PDF









Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aeberhard P., Butler V. P., Smith T. W., Haber E., Eng D. T., Brau J., Chalom A., Glatt B., Thébaut J. F., Delangenhagen B. Le traitement d'une intoxication digitalique massive (20 mg de digitoxine) par les anticorps anti-digoxine fractionnés (Fab). Arch Mal Coeur Vaiss. 1980 Dec;73(12):1471–1478. [PubMed] [Google Scholar]
- Bismuth C., Gaultier M., Conso F., Efthymiou M. L. Hyperkalemia in acute digitalis poisoning: prognostic significance and therapeutic implications. Clin Toxicol. 1973;6(2):153–162. doi: 10.3109/15563657308990513. [DOI] [PubMed] [Google Scholar]
- Brack C., Hirama M., Lenhard-Schuller R., Tonegawa S. A complete immunoglobulin gene is created by somatic recombination. Cell. 1978 Sep;15(1):1–14. doi: 10.1016/0092-8674(78)90078-8. [DOI] [PubMed] [Google Scholar]
- Burges R. A., Blackburn K. J. Adenyl cyclase and the differentiation of -adrenoreceptors. Nat New Biol. 1972 Feb 23;235(60):249–250. doi: 10.1038/newbio235249a0. [DOI] [PubMed] [Google Scholar]
- Croce C. M., Linnenbach A., Hall W., Steplewski Z., Koprowski H. Production of human hybridomas secreting antibodies to measles virus. Nature. 1980 Dec 4;288(5790):488–489. doi: 10.1038/288488a0. [DOI] [PubMed] [Google Scholar]
- Curd J., Smith T. W., Jaton J. C., Haber E. The isolation of digoxin-specific antibody and its use in reversing the effects of digoxin. Proc Natl Acad Sci U S A. 1971 Oct;68(10):2401–2406. doi: 10.1073/pnas.68.10.2401. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DEODHAR S. D., HAAS E., GOLDBLATT H. PRODUCTION OF ANTIRENIN TO HOMOLOGOUS RENIN AND ITS EFFECT OF EXPERIMENTAL RENAL HYPERTENSION. J Exp Med. 1964 Mar 1;119:425–432. doi: 10.1084/jem.119.3.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dzau V. J., Slater E. E., Haber E. Complete purification of dog renal renin. Biochemistry. 1979 Nov 13;18(23):5224–5228. doi: 10.1021/bi00590a029. [DOI] [PubMed] [Google Scholar]
- Early P., Huang H., Davis M., Calame K., Hood L. An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell. 1980 Apr;19(4):981–992. doi: 10.1016/0092-8674(80)90089-6. [DOI] [PubMed] [Google Scholar]
- Haber E. The Fifth Volhard Lecture. Specific inhibitors of renin. Clin Sci (Lond) 1980 Dec;59 (Suppl 6):7s–19s. doi: 10.1042/cs059007s. [DOI] [PubMed] [Google Scholar]
- Hess T., Stucki P., Barandun S., Scholtysik G., Riesen W. Treatment of a case of lanatoside C intoxication with digoxin-specific F(ab')2 antibody fragments. Am Heart J. 1979 Dec;98(6):767–771. doi: 10.1016/0002-8703(79)90476-9. [DOI] [PubMed] [Google Scholar]
- Hochman J., Inbar D., Givol D. An active antibody fragment (Fv) composed of the variable portions of heavy and light chains. Biochemistry. 1973 Mar 13;12(6):1130–1135. doi: 10.1021/bi00730a018. [DOI] [PubMed] [Google Scholar]
- Kahn C. R. Membrane receptors for hormones and neurotransmitters. J Cell Biol. 1976 Aug;70(2 Pt 1):261–286. doi: 10.1083/jcb.70.2.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katz A. M. Contractile proteins of the heart. Physiol Rev. 1970 Jan;50(1):63–158. doi: 10.1152/physrev.1970.50.1.63. [DOI] [PubMed] [Google Scholar]
- Khaw B. A., Beller G. A., Haber E., Smith T. W. Localization of cardiac myosin-specific antibody in myocardial infarction. J Clin Invest. 1976 Aug;58(2):439–446. doi: 10.1172/JCI108488. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Khaw B. A., Fallon F. T., Strauss H. W., Haber E. Myocardial infarct imaging of antibodies to canine cardiac myosin with indium-111-diethylenetriamine pentaacetic acid. Science. 1980 Jul 11;209(4453):295–297. doi: 10.1126/science.7384803. [DOI] [PubMed] [Google Scholar]
- Khaw B. A., Fallon J. T., Beller G. A., Haber E. Specificity of localization of myosin-specific antibody fragments in experimental myocardial infarction. Histologic, histochemical, autoradiographic and scintigraphic studies. Circulation. 1979 Dec;60(7):1527–1531. doi: 10.1161/01.cir.60.7.1527. [DOI] [PubMed] [Google Scholar]
- Khaw B. A., Gold H. K., Leinbach R. C., Fallon J. T., Strauss W., Pohost G. M., Haber E. Early imaging of experimental myocardial infarction by intracoronary administraion of 131I-labelled anticardiac myosin (Fab')2 fragments. Circulation. 1978 Dec;58(6):1137–1142. doi: 10.1161/01.cir.58.6.1137. [DOI] [PubMed] [Google Scholar]
- Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
- NISONOFF A. ENZYMATIC DIGESTION OF RABBIT GAMMA GLOBULIN AND ANTIBODY AND CHROMATOGRAPHY OF DIGESTION PRODUCTS. Methods Med Res. 1964;10:134–141. [PubMed] [Google Scholar]
- Ochs H. R., Smith T. W. Reversal of advanced digitoxin toxicity and modification of pharmacokinetics by specific antibodies and Fab fragments. J Clin Invest. 1977 Dec;60(6):1303–1313. doi: 10.1172/JCI108889. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Olsson L., Kaplan H. S. Human-human hybridomas producing monoclonal antibodies of predefined antigenic specificity. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5429–5431. doi: 10.1073/pnas.77.9.5429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rockson S. G., Homcy C. J., Haber E. Anti-alprenolol antibodies in the rabbit. A new probe for the study of beta-adrenergic receptor interaction. Circ Res. 1980 Jun;46(6):808–813. doi: 10.1161/01.res.46.6.808. [DOI] [PubMed] [Google Scholar]
- Sakano H., Kurosawa Y., Weigert M., Tonegawa S. Identification and nucleotide sequence of a diversity DNA segment (D) of immunoglobulin heavy-chain genes. Nature. 1981 Apr 16;290(5807):562–565. doi: 10.1038/290562a0. [DOI] [PubMed] [Google Scholar]
- Schreiber A. B., Couraud P. O., Andre C., Vray B., Strosberg A. D. Anti-alprenolol anti-idiotypic antibodies bind to beta-adrenergic receptors and modulate catecholamine-sensitive adenylate cyclase. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7385–7389. doi: 10.1073/pnas.77.12.7385. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seidman J. G., Leder A., Nau M., Norman B., Leder P. Antibody diversity. Science. 1978 Oct 6;202(4363):11–17. doi: 10.1126/science.99815. [DOI] [PubMed] [Google Scholar]
- Seidman J. G., Max E. E., Leder P. A kappa-immunoglobulin gene is formed by site-specific recombination without further somatic mutation. Nature. 1979 Aug 2;280(5721):370–375. doi: 10.1038/280370a0. [DOI] [PubMed] [Google Scholar]
- Smith T. W., Butler V. P., Jr, Haber E. Characterization of antibodies of high affinity and specificity for the digitalis glycoside digoxin. Biochemistry. 1970 Jan 20;9(2):331–337. doi: 10.1021/bi00804a020. [DOI] [PubMed] [Google Scholar]
- Smith T. W., Haber E., Yeatman L., Butler V. P., Jr Reversal of advanced digoxin intoxication with Fab fragments of digoxin-specific antibodies. N Engl J Med. 1976 Apr 8;294(15):797–800. doi: 10.1056/NEJM197604082941501. [DOI] [PubMed] [Google Scholar]
- Smith T. W., Lloyd B. L., Spicer N., Haber E. Immunogenicity and kinetics of distribution and elimination of sheep digoxin-specific IgG and Fab fragments in the rabbit and baboon. Clin Exp Immunol. 1979 Jun;36(3):384–396. [PMC free article] [PubMed] [Google Scholar]
- WAKERLIN G. E. Antibodies to renin as proof of the pathogenesis of sustained renal hypertension. Circulation. 1958 Apr;17(4 Pt 2):653–657. doi: 10.1161/01.cir.17.4.653. [DOI] [PubMed] [Google Scholar]
- Weigert M., Gatmaitan L., Loh E., Schilling J., Hood L. Rearrangement of genetic information may produce immunoglobulin diversity. Nature. 1978 Dec 21;276(5690):785–790. doi: 10.1038/276785a0. [DOI] [PubMed] [Google Scholar]
- Wrenn S., Haber E. An antibody specific for the propranolol binding site of cardiac muscle. J Biol Chem. 1979 Jul 25;254(14):6577–6582. [PubMed] [Google Scholar]
- Yang H. Y., Erdös E. G., Levin Y. A dipeptidyl carboxypeptidase that converts angiotensin I and inactivates bradykinin. Biochim Biophys Acta. 1970 Aug 21;214(2):374–376. doi: 10.1016/0005-2795(70)90017-6. [DOI] [PubMed] [Google Scholar]



