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

F. Poccia, P. Piselli, S. Di Cesare, S. Bach, V. Colizzi, M. Mattei, A. Bolognesi, F. Stirpe

Research output: Contribution to journalArticlepeer-review

Abstract

The expression of heat shock proteins (HSP) of the 65kD family (groEL) has been observed by flow cytometry using murine monoclonal antibody (MoAb) anti-HSP 65kD (ML30) on the surface of B (Daudi) or T (H9) lymphoma cells, on a moncyte 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 IgG, immunotoxin was also performed. With this method a human serum positive for HSP65-antibodies was tested using anti-human IgG 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.

Original languageEnglish
Pages (from-to)427-432
Number of pages6
JournalBritish Journal of Cancer
Volume66
Issue number3
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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