Immunotoxin-mediated inhibition of chronic lymphocytic leukemia cell proliferations in humans

S. Siena, M. Bregni, A. Formosa, B. Brando, P. Marenco, D. A. Lappi, G. Bonadonna, A. M. Gianni

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Abstract

We evaluated the cytotoxicity of the immunotoxin OKT1-SAP on fresh B-chronic lymphocytic leukemia (B-CLL) cells from 31 consecutive patients. OKT1-SAP comprised the OKT1 (CD5) monoclonal antibody disulfide linked to saporin-6 (SAP) ribosome-inactivating protein from the plant Saponaria officinalis. The effect of OKT1-SAP on target CD5-positive B-CLL cells was estimated using an in vitro proliferation inhibition assay in which control or OKT1-SAP-treated B-CLL cells were induced to proliferate by sequential stimulation with insolubilized anti-C3b receptor CB04 (CD35) antibody and low molecular weight B-cell growth factor. In 90% of patients, OKT1-SAP specifically suppressed B-CLL cell proliferation in a dose-related manner (50% inhibitory concentration, 4.0-6.8 nM). Taken together the findings reported in this article provide information relevant to the clinical development of immunotoxins because: (a) the in vitro conditions under which B-CLL cell proliferation is inhibited by OKT1-SAP are achievable in vivo without nonspecific toxicity according to our previous toxicology and pharmacokinetic studies in primates; and (b) the B-CLL cell proliferation inhibition assay described here provides a basis for future comparative studies.

Original languageEnglish
Pages (from-to)3328-3332
Number of pages5
JournalCancer Research
Volume49
Issue number12
Publication statusPublished - 1989

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Siena, S., Bregni, M., Formosa, A., Brando, B., Marenco, P., Lappi, D. A., Bonadonna, G., & Gianni, A. M. (1989). Immunotoxin-mediated inhibition of chronic lymphocytic leukemia cell proliferations in humans. Cancer Research, 49(12), 3328-3332.