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 pharmacokinetics studies in primates; and (b) the B-CLL cell proliferation inhibition assay described here provides a basis for future comparative studies.

Immunotoxin-mediated inhibition of chronic lymphocytic leukemia cell proliferation in humans / S. Siena, M. Bregni, A. Formosa, B. Brando, P. Marenco, D. A. Lappi, G. Bonadonna, A. M. Gianni. - In: CANCER RESEARCH. - ISSN 0008-5472. - 49:12(1989 Jun 15), pp. 3328-32-3332.

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

S. Siena;A.M. Gianni
1989

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 pharmacokinetics studies in primates; and (b) the B-CLL cell proliferation inhibition assay described here provides a basis for future comparative studies.
Humans; Aged; Plant Proteins; Immunotoxins; Antibodies, Monoclonal; Tumor Cells, Cultured; Leukemia, Lymphocytic, Chronic, B-Cell; Kinetics; Binding, Competitive; N-Glycosyl Hydrolases; Ribosome Inactivating Proteins, Type 1; Middle Aged; Antineoplastic Agents, Phytogenic; DNA Replication; Female; Male; Cell Division
Settore MED/06 - Oncologia Medica
15-giu-1989
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/182107
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