Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1992 Sep;66(3):427–432. doi: 10.1038/bjc.1992.291

Recognition and killing of tumour cells expressing heat shock protein 65 kD with immunotoxins containing saporin.

F Poccia 1, P Piselli 1, S Di Cesare 1, S Bach 1, V Colizzi 1, M Mattei 1, A Bolognesi 1, F Stirpe 1
PMCID: PMC1977954  PMID: 1520580

Abstract

The expression of heat shock proteins (HSP) of the 65 kD family (groEL) has been observed by flow cytometry using murine monoclonal antibody (MoAb) anti-HSP 65 kD (ML30) on the surface of B (Daudi) or T (H9) lymphoma cells, on a monocyte cell line (U937) and also on a primary culture of a human pancreatic carcinoma (HPC). Moreover, the MoAb ML30 was coupled to Saporin 6, a ribosome-inactivating protein recovered from the seeds of Saponaria officinalis, to kill HSP-expressing cells with a specific immunotoxin. An indirect method using first MoAb ML30 and then anti-mouse IgG1 immunotoxin was also performed. With this method a human serum positive for HSP65-antibodies was tested using anti-human IgG1 or IgM immunotoxins. All cell lines were inhibited when preincubated with the specific immunotoxin directed to HSP65 (ML30 SO6), although H9 cells were susceptible to immunotoxin only after thermal stress. Daudi and HPC cells were inhibited both after long-term culture and when freshly explanted from SCID mice. Proliferation of the U937 monocytic cell line, that constitutively expresses high levels of HSP65 on the surface (as determined by flow cytometry), was completely inhibited (100% inhibition) by the ML30 SO6. However, not all tumour cells constitutively express high levels of surface HSP65, as determined by cytometric analysis. For this reason it was not always possible to obtain complete inhibition of cellular proliferation.

Full text

PDF
427

Selected References

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

  1. Barbieri L., Bolognesi A., Dinota A., Lappi D. A., Soria M., Tazzari P. L., Stirpe F. Selective killing of CD4+ and CD8+ cells with immunotoxins containing saporin. Scand J Immunol. 1989 Sep;30(3):369–372. doi: 10.1111/j.1365-3083.1989.tb01223.x. [DOI] [PubMed] [Google Scholar]
  2. Bensaude O., Morange M. Spontaneous high expression of heat-shock proteins in mouse embryonal carcinoma cells and ectoderm from day 8 mouse embryo. EMBO J. 1983;2(2):173–177. doi: 10.1002/j.1460-2075.1983.tb01401.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bolognesi A., Barbieri L., Carnicelli D., Abbondanza A., Cenini P., Falasca A. I., Dinota A., Stirpe F. Purification and properties of a new ribosome-inactivating protein with RNA N-glycosidase activity suitable for immunotoxin preparation from the seeds of Momordica cochinchinensis. Biochim Biophys Acta. 1989 Dec 8;993(2-3):287–292. doi: 10.1016/0304-4165(89)90178-5. [DOI] [PubMed] [Google Scholar]
  4. Bosma G. C., Custer R. P., Bosma M. J. A severe combined immunodeficiency mutation in the mouse. Nature. 1983 Feb 10;301(5900):527–530. doi: 10.1038/301527a0. [DOI] [PubMed] [Google Scholar]
  5. Evans D. J., Norton P., Ivanyi J. Distribution in tissue sections of the human groEL stress-protein homologue. APMIS. 1990 May;98(5):437–441. doi: 10.1111/j.1699-0463.1990.tb01055.x. [DOI] [PubMed] [Google Scholar]
  6. Finlay C. A., Hinds P. W., Tan T. H., Eliyahu D., Oren M., Levine A. J. Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life. Mol Cell Biol. 1988 Feb;8(2):531–539. doi: 10.1128/mcb.8.2.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fisch P., Malkovsky M., Braakman E., Sturm E., Bolhuis R. L., Prieve A., Sosman J. A., Lam V. A., Sondel P. M. Gamma/delta T cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatibility complex-restricted cytolysis. J Exp Med. 1990 May 1;171(5):1567–1579. doi: 10.1084/jem.171.5.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ivanyi J., Sinha S., Aston R., Cussell D., Keen M., Sengupta U. Definition of species specific and cross-reactive antigenic determinants of Mycobacterium leprae using monoclonal antibodies. Clin Exp Immunol. 1983 Jun;52(3):528–536. [PMC free article] [PubMed] [Google Scholar]
  9. Kaufmann S. H. Heat shock proteins and the immune response. Immunol Today. 1990 Apr;11(4):129–136. doi: 10.1016/0167-5699(90)90050-j. [DOI] [PubMed] [Google Scholar]
  10. Koskinen P. J., Sistonen L., Evan G., Morimoto R., Alitalo K. Nuclear colocalization of cellular and viral myc proteins with HSP70 in myc-overexpressing cells. J Virol. 1991 Feb;65(2):842–851. doi: 10.1128/jvi.65.2.842-851.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. La Thangue N. B., Latchman D. S. A cellular protein related to heat-shock protein 90 accumulates during herpes simplex virus infection and is overexpressed in transformed cells. Exp Cell Res. 1988 Sep;178(1):169–179. doi: 10.1016/0014-4827(88)90388-6. [DOI] [PubMed] [Google Scholar]
  12. Lindquist S., Craig E. A. The heat-shock proteins. Annu Rev Genet. 1988;22:631–677. doi: 10.1146/annurev.ge.22.120188.003215. [DOI] [PubMed] [Google Scholar]
  13. Mosier D. E., Gulizia R. J., Baird S. M., Wilson D. B. Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature. 1988 Sep 15;335(6187):256–259. doi: 10.1038/335256a0. [DOI] [PubMed] [Google Scholar]
  14. Munk M. E., Schoel B., Modrow S., Karr R. W., Young R. A., Kaufmann S. H. T lymphocytes from healthy individuals with specificity to self-epitopes shared by the mycobacterial and human 65-kilodalton heat shock protein. J Immunol. 1989 Nov 1;143(9):2844–2849. [PubMed] [Google Scholar]
  15. Nevins J. R. Induction of the synthesis of a 70,000 dalton mammalian heat shock protein by the adenovirus E1A gene product. Cell. 1982 Jul;29(3):913–919. doi: 10.1016/0092-8674(82)90453-6. [DOI] [PubMed] [Google Scholar]
  16. Pechan P. M. Heat shock proteins and cell proliferation. FEBS Lett. 1991 Mar 11;280(1):1–4. doi: 10.1016/0014-5793(91)80190-e. [DOI] [PubMed] [Google Scholar]
  17. Ralston R. Complementation of transforming domains in E1a/myc chimaeras. Nature. 1991 Oct 31;353(6347):866–868. doi: 10.1038/353866a0. [DOI] [PubMed] [Google Scholar]
  18. Srivastava P. K., Maki R. G. Stress-induced proteins in immune response to cancer. Curr Top Microbiol Immunol. 1991;167:109–123. doi: 10.1007/978-3-642-75875-1_7. [DOI] [PubMed] [Google Scholar]
  19. Stirpe F., Barbieri L., Battelli M. G., Soria M., Lappi D. A. Ribosome-inactivating proteins from plants: present status and future prospects. Biotechnology (N Y) 1992 Apr;10(4):405–412. doi: 10.1038/nbt0492-405. [DOI] [PubMed] [Google Scholar]
  20. Tazzari P. L., Barbieri L., Gobbi M., Dinota A., Rizzi S., Bontadini A., Pession A., Tura S., Stirpe F. An immunotoxin containing a rat IgM monoclonal antibody (Campath 1) and saporin 6: effect on T lymphocytes and hemopoietic cells. Cancer Immunol Immunother. 1988;26(3):231–236. doi: 10.1007/BF00199934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ullrich S. J., Robinson E. A., Law L. W., Willingham M., Appella E. A mouse tumor-specific transplantation antigen is a heat shock-related protein. Proc Natl Acad Sci U S A. 1986 May;83(10):3121–3125. doi: 10.1073/pnas.83.10.3121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wand-Württenberger A., Schoel B., Ivanyi J., Kaufmann S. H. Surface expression by mononuclear phagocytes of an epitope shared with mycobacterial heat shock protein 60. Eur J Immunol. 1991 Apr;21(4):1089–1092. doi: 10.1002/eji.1830210437. [DOI] [PubMed] [Google Scholar]

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

RESOURCES