Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Sep;89(3):341–346. doi: 10.1111/j.1365-2249.1992.tb06959.x

A comparison of anti-lymphocyte immunotoxins containing different ribosome-inactivating proteins and antibodies.

A Bolognesi 1, P L Tazzari 1, C Tassi 1, G Gromo 1, M Gobbi 1, F Stirpe 1
PMCID: PMC1554454  PMID: 1516253

Abstract

Immunotoxins were prepared with several single-chain ribosome-inactivating proteins (RIPs type 1) and with the A-chain of ricin linked to the F(ab')2 fragment of sheep anti-mouse IgG. The cytotoxic activity of these conjugates was tested on human lymphocytes pretreated with an anti-CD3 murine MoAb. The immunotoxins inhibited DNA synthesis in phytohaemagglutinin (PHA)-stimulated lymphocytes with IC50S (concentrations causing 50% inhibition) ranging from 8.9 x 10(-13) to 5.7 x 10(-11) M (immunotoxins containing dianthin 32, saporin, pokeweed antiviral protein from seeds (PAP-S), bryodin, momordin, momorcochin, and trichokirin), 1 x 10(-8) M (immunotoxin containing gelonin) and 5 x 10(-9) M (immunotoxin containing ricin A-chain). The immunotoxin containing saporin linked to the anti-mouse IgG F(ab')2 fragment was also highly toxic to human lymphocytes pretreated with anti-CD2, -CD3, -CD5 and -CD45 MoAbs, with IC50S less than or equal to 10(-11) M. Immunotoxins were prepared also with saporin linked to MoAbs against various CD antigens. The immunotoxin prepared with the anti-CD3 antibody had the highest specific cytotoxicity to human lymphocytes.

Full text

PDF
341

Images in this article

344Fig. 2
on p.344

Selected References

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

  1. ALLEN E. H., SCHWEET R. S. Synthesis of hemoglobin in a cell-free system. I. Properties of the complete system. J Biol Chem. 1962 Mar;237:760–767. [PubMed] [Google Scholar]
  2. Brust S., Filipp G., Hofmann U., Kalies I., Peper K., Rajki K., Sterz R. K., Trommer W. E. Antigen-gelonin conjugates. Preparation and application in experimental myasthenia gravis. Biol Chem Hoppe Seyler. 1987 Aug;368(8):991–999. doi: 10.1515/bchm3.1987.368.2.991. [DOI] [PubMed] [Google Scholar]
  3. Casellas P., Bourrie B. J., Gros P., Jansen F. K. Kinetics of cytotoxicity induced by immunotoxins. Enhancement by lysosomotropic amines and carboxylic ionophores. J Biol Chem. 1984 Aug 10;259(15):9359–9364. [PubMed] [Google Scholar]
  4. Casellas P., Dussossoy D., Falasca A. I., Barbieri L., Guillemot J. C., Ferrara P., Bolognesi A., Cenini P., Stirpe F. Trichokirin, a ribosome-inactivating protein from the seeds of Trichosanthes kirilowii Maximowicz. Purification, partial characterization and use for preparation of immunotoxins. Eur J Biochem. 1988 Oct 1;176(3):581–588. doi: 10.1111/j.1432-1033.1988.tb14317.x. [DOI] [PubMed] [Google Scholar]
  5. Dinota A., Barbieri L., Gobbi M., Tazzari P. L., Rizzi S., Bontadini A., Bolognesi A., Tura S., Stirpe F. An immunotoxin containing momordin suitable for bone marrow purging in multiple myeloma patients. Br J Cancer. 1989 Sep;60(3):315–319. doi: 10.1038/bjc.1989.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fodstad O., Kvalheim G., Pihl A., Godal A., Funderud S. New indirect approach to the therapeutic use of immunotoxins. J Natl Cancer Inst. 1988 May 18;80(6):439–443. doi: 10.1093/jnci/80.6.439. [DOI] [PubMed] [Google Scholar]
  7. Foxwell B. M., Donovan T. A., Thorpe P. E., Wilson G. The removal of carbohydrates from ricin with endoglycosidases H, F and D and alpha-mannosidase. Biochim Biophys Acta. 1985 Jun 18;840(2):193–203. doi: 10.1016/0304-4165(85)90119-9. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Goldmacher V. S., Blättler W. A., Lambert J. M., McIntyre G., Stewart J. Cytotoxicity of gelonin conjugated to targeting molecules: effects of weak amines, monensin, adenovirus, and adenoviral capsid proteins penton, hexon, and fiber. Mol Pharmacol. 1989 Nov;36(5):818–822. [PubMed] [Google Scholar]
  10. Lambert J. M., Blättler W. A., McIntyre G. D., Goldmacher V. S., Scott C. F., Jr Immunotoxins containing single-chain ribosome-inactivating proteins. Cancer Treat Res. 1988;37:175–209. doi: 10.1007/978-1-4613-1083-9_12. [DOI] [PubMed] [Google Scholar]
  11. Lambert J. M., Senter P. D., Yau-Young A., Blättler W. A., Goldmacher V. S. 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] [Google Scholar]
  12. Martin P. J., Hansen J. A., Vitetta E. S. A ricin A chain-containing immunotoxin that kills human T lymphocytes in vitro. Blood. 1985 Oct;66(4):908–912. [PubMed] [Google Scholar]
  13. Ozawa S., Ueda M., Ando N., Abe O., Minoshima S., Shimizu N. Selective killing of squamous carcinoma cells by an immunotoxin that recognizes the EGF receptor. Int J Cancer. 1989 Jan 15;43(1):152–157. doi: 10.1002/ijc.2910430128. [DOI] [PubMed] [Google Scholar]
  14. Siena S., Bregni M., Formosa A., Martineau D., Lappi D. A., Bonadonna G., Gianni A. M. Evaluation of antihuman T lymphocyte saporin immunotoxins potentially useful in human transplantation. Transplantation. 1988 Nov;46(5):747–753. doi: 10.1097/00007890-198811000-00023. [DOI] [PubMed] [Google Scholar]
  15. Siena S., Lappi D. A., Bregni M., Formosa A., Villa S., Soria M., Bonadonna G., Gianni A. M. Synthesis and characterization of an antihuman T-lymphocyte saporin immunotoxin (OKT1-SAP) with in vivo stability into nonhuman primates. Blood. 1988 Aug;72(2):756–765. [PubMed] [Google Scholar]
  16. Singh V., Sairam M. R., Bhargavi G. N., Akhras R. G. Hormonotoxins. Preparation and characterization of ovine luteinizing hormone-gelonin conjugate. J Biol Chem. 1989 Feb 25;264(6):3089–3095. [PubMed] [Google Scholar]
  17. Sivam G., Pearson J. W., Bohn W., Oldham R. K., Sadoff J. C., Morgan A. C., 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] [Google Scholar]
  18. Stirpe F., Barbieri L. Ribosome-inactivating proteins up to date. FEBS Lett. 1986 Jan 20;195(1-2):1–8. doi: 10.1016/0014-5793(86)80118-1. [DOI] [PubMed] [Google Scholar]
  19. Stirpe F., Gasperi-Campani A., Barbieri L., Falasca A., Abbondanza A., Stevens W. A. Ribosome-inactivating proteins from the seeds of Saponaria officinalis L. (soapwort), of Agrostemma githago L. (corn cockle) and of Asparagus officinalis L. (asparagus), and from the latex of Hura crepitans L. (sandbox tree). Biochem J. 1983 Dec 15;216(3):617–625. doi: 10.1042/bj2160617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Tazzari P. L., Gobbi M., Dinota A., Bontadini A., Grassi G., Cerato C., Cavo M., Pileri S., Caligaris-Cappio F., Tura S. Normal and neoplastic plasma cell membrane phenotype: studies with new monoclonal antibodies. Clin Exp Immunol. 1987 Oct;70(1):192–200. [PMC free article] [PubMed] [Google Scholar]
  21. Thorpe P. E., Brown A. N., Ross W. C., Cumber A. J., Detre S. I., Edwards D. C., Davies A. J., 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. doi: 10.1111/j.1432-1033.1981.tb05356.x. [DOI] [PubMed] [Google Scholar]
  22. Till M., May R. D., Uhr J. W., Thorpe P. E., Vitetta E. S. An assay that predicts the ability of monoclonal antibodies to form potent ricin A chain-containing immunotoxins. Cancer Res. 1988 Mar 1;48(5):1119–1123. [PubMed] [Google Scholar]
  23. Weltman J. K., Pedroso P., Johnson S. A., Davignon D., Fast L. D., Leone L. A. Rapid screening with indirect immunotoxin for monoclonal antibodies against human small cell lung cancer. Cancer Res. 1987 Nov 1;47(21):5552–5556. [PubMed] [Google Scholar]
  24. Wiels J., Junqua S., Dujardin P., Le Pecq J. B., Tursz T. Properties of immunotoxins against a glycolipid antigen associated with Burkitt's lymphoma. Cancer Res. 1984 Jan;44(1):129–133. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES