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. 1980 Sep;77(9):5419–5423. doi: 10.1073/pnas.77.9.5419

Selective killing of normal or neoplastic B cells by antibodies coupled to the A chain of ricin.

K A Krolick, C Villemez, P Isakson, J W Uhr, E S Vitetta
PMCID: PMC350070  PMID: 6968912

Abstract

Highly specific antibodies (affinity-purified or hybridoma) directed against cell surface immunoglobulins on normal or neoplastic murine B lymphocytes were covalently coupled to the A chain of the plant toxin ricin. Such conjugates containing antibodies specific for IgM, for either of the two allotypes of IgD, or for the idiotype of the B cell tumor BCL1 rapidly bound in vitro to cells expressing the corresponding surface antigen and inhibited protein synthesis in such cells. The results demonstrate that A chain-coupled anti-idiotype antibody may be useful as a tumor-specific cytotoxic agent.

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Selected References

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

  1. Carlsson J., Drevin H., Axén R. Protein thiolation and reversible protein-protein conjugation. N-Succinimidyl 3-(2-pyridyldithio)propionate, a new heterobifunctional reagent. Biochem J. 1978 Sep 1;173(3):723–737. doi: 10.1042/bj1730723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chang T. M., Dazord A., Neville D. M., Jr Artificial hybrid protein containing a toxic protein fragment and a cell membrane receptor-binding moiety in a disulfide conjugate. II. Biochemical and biologic properties of diphtheria toxin fragment A-S-S-human placental lactogen. J Biol Chem. 1977 Feb 25;252(4):1515–1522. [PubMed] [Google Scholar]
  3. Cuatrecasas P. Affinity chromatography. Annu Rev Biochem. 1971;40:259–278. doi: 10.1146/annurev.bi.40.070171.001355. [DOI] [PubMed] [Google Scholar]
  4. Fu S. M., Winchester R. J., Kunkel H. G. Similar idiotypic specificity for the membrane IgD and IgM of human B lymphocytes. J Immunol. 1975 Jan;114(1 Pt 1):250–252. [PubMed] [Google Scholar]
  5. Ghose T., Blair A. H. Antibody-linked cytotoxic agents in the treatment of cancer: current status and future prospects. J Natl Cancer Inst. 1978 Sep;61(3):657–676. [PubMed] [Google Scholar]
  6. Gilliland D. G., Collier R. J., Moehring J. M., Moehring T. J. Chimeric toxins: toxic, disulfide-linked conjugate of concanavalin A with fragment A from diphtheria toxin. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5319–5323. doi: 10.1073/pnas.75.11.5319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Isakson P. C., Krolick K. A., Uhr J. W., Vitetta E. S. The effect of anti-immunoglobulin antibodies on the in vitro proliferation and differentiation of normal and neoplastic murineB cells. J Immunol. 1980 Aug;125(2):886–892. [PubMed] [Google Scholar]
  8. Kennett R. H. Cell fusion. Methods Enzymol. 1979;58:345–359. doi: 10.1016/s0076-6879(79)58149-x. [DOI] [PubMed] [Google Scholar]
  9. Krolick K. A., Isakson P. C., Uhr J. W., Vitetta E. S. Murine B cell leukemia (BCL1): organ distribution and kinetics of growth as determined by fluorescence analysis with an anti-idiotypic antibody. J Immunol. 1979 Nov;123(5):1928–1935. [PubMed] [Google Scholar]
  10. 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]
  11. Lynes M. A., Lanier L. L., Babcock G. F., Wettstein P. J., Haughton G. Antigen-induced murine B cell lymphomas. I. Induction and characterization of CH1 and CH2. J Immunol. 1978 Dec;121(6):2352–2357. [PubMed] [Google Scholar]
  12. Masuho Y., Hara T., Noguchi T. Preparation of a hybrid of fragment Fab' of antibody and fragment A of diphtheria toxin and its cytotoxicity. Biochem Biophys Res Commun. 1979 Sep 12;90(1):320–326. doi: 10.1016/0006-291x(79)91627-9. [DOI] [PubMed] [Google Scholar]
  13. Moolten F. L., Capparell N. J., Zajdel S. H., Cooperband S. R. Antitumor effects of antibody-diphtheria toxin conjugates. II. Immunotherapy with conjugates directed against tumor antigens induced by simian virus 40. J Natl Cancer Inst. 1975 Aug;55(2):473–477. [PubMed] [Google Scholar]
  14. Oeltmann T. N., Heath E. C. A hybrid protein containing the toxic subunit of ricin and the cell-specific subunit of human chorionic gonadotropin. II. Biologic properties. J Biol Chem. 1979 Feb 25;254(4):1028–1032. [PubMed] [Google Scholar]
  15. Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
  16. Olsnes S., Pihl A. Different biological properties of the two constituent peptide chains of ricin, a toxic protein inhibiting protein synthesis. Biochemistry. 1973 Jul 31;12(16):3121–3126. doi: 10.1021/bi00740a028. [DOI] [PubMed] [Google Scholar]
  17. Pappenheimer A. M., Jr, Gill D. M. Diphtheria. Science. 1973 Oct 26;182(4110):353–358. doi: 10.1126/science.182.4110.353. [DOI] [PubMed] [Google Scholar]
  18. Ross W. C., Thorpe P. E., Cumber A. J., Edwards D. C., Hinson C. A., Davies A. J. Increased toxicity of diphtheria toxin for human lymphoblastoid cells following covalent linkage to anti-(human lymphocyte) globulin or its F(ab')2 fragment. Eur J Biochem. 1980 Mar;104(2):381–390. doi: 10.1111/j.1432-1033.1980.tb04438.x. [DOI] [PubMed] [Google Scholar]
  19. Uchida T., Yamaizumi M., Mekada E., Okada Y., Tsuda M., Kurokawa T., Sugino Y. Reconstitution of hybrid toxin from Fragment A of diphtheria toxin and a subunit of Wistaria floribunda lectin. J Biol Chem. 1978 Sep 25;253(18):6307–6310. [PubMed] [Google Scholar]
  20. Vitetta E. S., Yuan D., Krolick K., Isakson P., Knapp M., Slavin S., Strober S. Characterization of the spontaneous murine B cell leukemia (BCL1). III. Evidence for monoclonality by using an anti-idiotype antibody. J Immunol. 1979 May;122(5):1649–1654. [PubMed] [Google Scholar]
  21. Vitetta E., Krolick K. Allelic exclusion of IgD allotypes on murine B cells. J Immunol. 1980 Jun;124(6):2988–2990. [PubMed] [Google Scholar]

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