B-cell restricted saporin immunotoxins: Activity against B-cell lines and chronic lymphocytic leukemia cells

M. Bregni, S. Siena, A. Formosa, D. A. Lappi, D. Martineau, F. Malavasi, B. Dorken, G. Bonadonna, A. M. Gianni

Research output: Contribution to journalArticle

Abstract

B cell-restricted immunotoxins were constructed by conjugating anti-B monoclonal antibodies to saporin, the major ribosome inactivating protein from the seeds of the plant Saponaria officinalis. HD37-SAP is directed against CD19, the broadest B cell-specific determinant. HD39-SAP and HD6-SAP recognize two different epitopes on the CD22 molecule, an antigen present on the cell surface of B cells at late stages of differentiation. All three immunotoxins inhibited DNA synthesis and protein synthesis in target B lymphoma cells with a dose-related effect, in short incubation times and in the absence of potentiators. A clonogenic assay demonstrated that all immunotoxins could eliminate more than two logs of clonogenic malignant B cells with a two-hour incubation at concentrations not toxic to cells not bearing target antigens. The immunotoxin activity was evaluated by DNA synthesis inhibition in fresh B-chronic lymphocytic leukemia cells (B-CLL) stimulated to proliferate by incubation with an antibody specific for the receptor of C3b complement component (CR1) plus B cell growth factor. B-CLL cell DNA synthesis was actively inhibited by treatment at low immunotoxin concentration without need of potentiators. Immunotoxins exerted their effect also in whole blood of CLL patients under conditions achievable in vivo. We conclude that B cell-restricted immunotoxins HD37-SAP, HD39-SAP, and HD6-SAP are good candidates for in vivo therapy of B-cell malignancies.

Original languageEnglish
Pages (from-to)753-762
Number of pages10
JournalBlood
Volume73
Issue number3
Publication statusPublished - 1989

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Immunotoxins
B-Cell Chronic Lymphocytic Leukemia
B-Lymphocytes
Cells
Cell Line
Sialic Acid Binding Ig-like Lectin 2
Saponaria
DNA
Bearings (structural)
Complement 3b Receptors
Ribosome Inactivating Proteins
Complement C3b
Antigens
Complement Receptors
Poisons
Cell growth
B-Cell Lymphoma
saporin
Seed
Epitopes

ASJC Scopus subject areas

  • Hematology

Cite this

Bregni, M., Siena, S., Formosa, A., Lappi, D. A., Martineau, D., Malavasi, F., ... Gianni, A. M. (1989). B-cell restricted saporin immunotoxins: Activity against B-cell lines and chronic lymphocytic leukemia cells. Blood, 73(3), 753-762.

B-cell restricted saporin immunotoxins : Activity against B-cell lines and chronic lymphocytic leukemia cells. / Bregni, M.; Siena, S.; Formosa, A.; Lappi, D. A.; Martineau, D.; Malavasi, F.; Dorken, B.; Bonadonna, G.; Gianni, A. M.

In: Blood, Vol. 73, No. 3, 1989, p. 753-762.

Research output: Contribution to journalArticle

Bregni, M, Siena, S, Formosa, A, Lappi, DA, Martineau, D, Malavasi, F, Dorken, B, Bonadonna, G & Gianni, AM 1989, 'B-cell restricted saporin immunotoxins: Activity against B-cell lines and chronic lymphocytic leukemia cells', Blood, vol. 73, no. 3, pp. 753-762.
Bregni M, Siena S, Formosa A, Lappi DA, Martineau D, Malavasi F et al. B-cell restricted saporin immunotoxins: Activity against B-cell lines and chronic lymphocytic leukemia cells. Blood. 1989;73(3):753-762.
Bregni, M. ; Siena, S. ; Formosa, A. ; Lappi, D. A. ; Martineau, D. ; Malavasi, F. ; Dorken, B. ; Bonadonna, G. ; Gianni, A. M. / B-cell restricted saporin immunotoxins : Activity against B-cell lines and chronic lymphocytic leukemia cells. In: Blood. 1989 ; Vol. 73, No. 3. pp. 753-762.
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