Activity of a monoclonal antibody-saporin-6 conjugate against B-lymphoma cells

M. Bregni, D. A. Lappi, S. Siena, A. Formosa, S. Villa, M. Soria, G. Bonadonna, A. M. Gianni

Research output: Contribution to journalArticle

Abstract

A monoclonal antibody reactive with the immunoglobulin heavy chain (TEC IgM) has been conjugated to saporin-6 (SAP), which is the major ribosome-inactivating protein from the seeds of the plant Saponaria officinalis. Studies with Burkitt's lymphoma cell line Bjab 113 demonstrate that this immunotoxin is capable of killing 3 logs (99.9%) of clonogenic lymphoma cells after a 2-hour incubation. The presence of human bone marrow inhibits the activity of the conjugate. However, full potency of TEC IgM-SAP immunotoxin is restored by adding 1 mM amantadine to the incubation medium. The reaction is highly specific and is inhibited by the presence of excess anti-μ-antibody or human serum. Clonal growth of Burkitt's lymphoma cell lines is inhibited to a lesser extent by the immunotoxin. The presence of surface IgM on the different cell lines is directly correlated to target cell killing by TEC IgM-SAP. Isolation of Bjab 113 clones surviving treatment demonstrates that only a minority are truly resistant and that the others randomly escape the treatment. The highly potent and specific activity of this conjugate in the presence of bone marrow buffy coat and its exceptionally rapid onset of action make this conjugate a good candidate for the ex vivo elimination of neoplastic cells from the bone marrow of non-Hodgkin's lymphoma patients.

Original languageEnglish
Pages (from-to)511-517
Number of pages7
JournalJournal of the National Cancer Institute
Volume80
Issue number7
Publication statusPublished - 1988

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging

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    Bregni, M., Lappi, D. A., Siena, S., Formosa, A., Villa, S., Soria, M., Bonadonna, G., & Gianni, A. M. (1988). Activity of a monoclonal antibody-saporin-6 conjugate against B-lymphoma cells. Journal of the National Cancer Institute, 80(7), 511-517.