PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of brjcancerBJC HomepageBJC Advance online publicationBJC Current IssueSubmitting an article to BJCWeb feeds
 
Br J Cancer. 1988 November; 58(5): 558–561.
PMCID: PMC2246839

Selective cytotoxic activity of immunotoxins composed of a monoclonal anti-Thy 1.1 antibody and the ribosome-inactivating proteins bryodin and momordin.

Abstract

The ribosome-inactivating proteins, bryodin, from Bryonia dioica, and momordin, from Momordica charantia, were coupled by a disulphide bond to a monoclonal anti-Thy 1.1 antibody (OX7). Both immunotoxins were specifically cytotoxic to the Thy 1.1-expressing mouse lymphoma cell line AKR-A in vitro. The OX7-bryodin immunotoxins were the more powerfully toxic and reduced protein synthesis in AKR-A cells by 50% at a concentration of 1-4 x 10(-11) M as compared with 1 x 10(-9) M for the OX7-momordin immunotoxins. Neither of the immunotoxins was toxic to mouse lymphoma EL4 cells, which lack the Thy 1.1 antigen, at concentrations up to 3 x 10(-8) M. Further, bryodin and momordin immunotoxins made from an antibody (R10) of irrelevant specificity were without effect on AKR-A cells.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (841K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Barbieri L, Zamboni M, Lorenzoni E, Montanaro L, Sperti S, Stirpe F. Inhibition of protein synthesis in vitro by proteins from the seeds of Momordica charantia (bitter pear melon). Biochem J. 1980 Feb 15;186(2):443–452. [PubMed]
  • Blakey DC, Thorpe PE. Prevention of carbohydrate-mediated clearance of ricin-containing immunotoxins by the liver. Cancer Treat Res. 1988;37:457–473. [PubMed]
  • Blakey DC, Watson GJ, Knowles PP, Thorpe PE. Effect of chemical deglycosylation of ricin A chain on the in vivo fate and cytotoxic activity of an immunotoxin composed of ricin A chain and anti-Thy 1.1 antibody. Cancer Res. 1987 Feb 15;47(4):947–952. [PubMed]
  • Blythman HE, Casellas P, Gros O, Gros P, Jansen FK, Paolucci F, Pau B, Vidal H. Immunotoxins: hybrid molecules of monoclonal antibodies and a toxin subunit specifically kill tumour cells. Nature. 1981 Mar 12;290(5802):145–146. [PubMed]
  • Colombatti M, Nabholz M, Gros O, Bron C. Selective killing of target cells by antibody-ricin A chain or antibody-gelonin hybrid molecules: comparison of cytotoxic potency and use in immunoselection procedures. J Immunol. 1983 Dec;131(6):3091–3095. [PubMed]
  • Falasca A, Gasperi-Campani A, Abbondanza A, Barbieri L, Stirpe F. Properties of the ribosome-inactivating proteins gelonin, Momordica charantia inhibitor, and dianthins. Biochem J. 1982 Dec 1;207(3):505–509. [PubMed]
  • Glennie MJ, McBride HM, Stirpe F, Thorpe PE, Worth AT, Stevenson GT. Emergence of immunoglobulin variants following treatment of a B cell leukemia with an immunotoxin composed of antiidiotypic antibody and saporin. J Exp Med. 1987 Jul 1;166(1):43–62. [PMC free article] [PubMed]
  • Lambert JM, Senter PD, Yau-Young A, Blättler WA, Goldmacher VS. Purified immunotoxins that are reactive with human lymphoid cells. Monoclonal antibodies conjugated to the ribosome-inactivating proteins gelonin and the pokeweed antiviral proteins. J Biol Chem. 1985 Oct 5;260(22):12035–12041. [PubMed]
  • Letvin NL, Goldmacher VS, Ritz J, Yetz JM, Schlossman SF, Lambert JM. In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. In vivo stability of disulfide-linked immunotoxin conjugates. J Clin Invest. 1986 Mar;77(3):977–984. [PMC free article] [PubMed]
  • Mason DW, Williams AF. The kinetics of antibody binding to membrane antigens in solution and at the cell surface. Biochem J. 1980 Apr 1;187(1):1–20. [PubMed]
  • Masuho Y, Kishida K, Hara T. Targeting of the antiviral protein from Phytolacca americana with an antibody. Biochem Biophys Res Commun. 1982 Mar 30;105(2):462–469. [PubMed]
  • Ramakrishnan S, Houston LL. Comparison of the selective cytotoxic effects of immunotoxins containing ricin A chain or pokeweed antiviral protein and anti-Thy 1.1 monoclonal antibodies. Cancer Res. 1984 Jan;44(1):201–208. [PubMed]
  • Ramakrishnan S, Houston LL. Prevention of growth of leukemia cells in mice by monoclonal antibodies directed against Thy 1.1 antigen disulfide linked to two ribosomal inhibitors:pokeweed antiviral protein or ricin A chain. Cancer Res. 1984 Apr;44(4):1398–1404. [PubMed]
  • Ramakrishnan S, Houston LL. Immunological and biological stability of immunotoxins in vivo as studied by the clearance of disulfide-linked pokeweed antiviral protein-antibody conjugates from blood. Cancer Res. 1985 May;45(5):2031–2036. [PubMed]
  • Scott CF, Jr, Goldmacher VS, Lambert JM, Jackson JV, McIntyre GD. An immunotoxin composed of a monoclonal antitransferrin receptor antibody linked by a disulfide bond to the ribosome-inactivating protein gelonin: potent in vitro and in vivo effects against human tumors. J Natl Cancer Inst. 1987 Nov;79(5):1163–1172. [PubMed]
  • Scott CF, Jr, Lambert JM, Goldmacher VS, Blatter WA, Sobel R, Schlossman SF, Benacerraf B. The pharmacokinetics and toxicity of murine monoclonal antibodies and of gelonin conjugates of these antibodies. Int J Immunopharmacol. 1987;9(2):211–225. [PubMed]
  • Sivam G, Pearson JW, Bohn W, Oldham RK, Sadoff JC, Morgan AC., Jr Immunotoxins to a human melanoma-associated antigen: comparison of gelonin with ricin and other A chain conjugates. Cancer Res. 1987 Jun 15;47(12):3169–3173. [PubMed]
  • Stirpe F, Bailey S, Miller SP, Bodley JW. Modification of ribosomal RNA by ribosome-inactivating proteins from plants. Nucleic Acids Res. 1988 Feb 25;16(4):1349–1357. [PMC free article] [PubMed]
  • Stirpe F, Barbieri L. Ribosome-inactivating proteins up to date. FEBS Lett. 1986 Jan 20;195(1-2):1–8. [PubMed]
  • Stirpe F, Barbieri L, Battelli MG, Falasca AI, Abbondanza A, Lorenzoni E, Stevens WA. Bryodin, a ribosome-inactivating protein from the roots of Bryonia dioica L. (white bryony). Biochem J. 1986 Dec 15;240(3):659–665. [PubMed]
  • Thorpe PE, Blakey DC, Brown AN, Knowles PP, Knyba RE, Wallace PM, Watson GJ, Wawrzynczak EJ. Comparison of two anti-Thy 1.1-abrin A-chain immunotoxins prepared with different cross-linking agents: antitumor effects, in vivo fate, and tumor cell mutants. J Natl Cancer Inst. 1987 Nov;79(5):1101–1112. [PubMed]
  • Thorpe PE, Brown AN, Bremner JA, Jr, Foxwell BM, Stirpe F. An immunotoxin composed of monoclonal anti-Thy 1.1 antibody and a ribosome-inactivating protein from Saponaria officinalis: potent antitumor effects in vitro and in vivo. J Natl Cancer Inst. 1985 Jul;75(1):151–159. [PubMed]
  • Thorpe PE, Brown AN, Ross WC, Cumber AJ, Detre SI, Edwards DC, Davies AJ, Stirpe F. Cytotoxicity acquired by conjugation of an anti-Thy1.1 monoclonal antibody and the ribosome-inactivating protein, gelonin. Eur J Biochem. 1981 Jun 1;116(3):447–454. [PubMed]
  • Uckun FM, Ramakrishnan S, Houston LL. Increased efficiency in selective elimination of leukemia cells by a combination of a stable derivative of cyclophosphamide and a human B-cell-specific immunotoxin containing pokeweed antiviral protein. Cancer Res. 1985 Jan;45(1):69–75. [PubMed]
  • Wawrzynczak EJ, Thorpe PE. Effect of chemical linkage upon the stability and cytotoxic activity of A chain immunotoxins. Cancer Treat Res. 1988;37:239–251. [PubMed]
  • Wiels J, Junqua S, Dujardin P, Le Pecq JB, Tursz T. Properties of immunotoxins against a glycolipid antigen associated with Burkitt's lymphoma. Cancer Res. 1984 Jan;44(1):129–133. [PubMed]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK