1. CD38 as a target of IB4 mAb carrying saporin-S6: design of an immunotoxin for ex vivo depletion of hematological CD38+ neoplasia.
- Author
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Bolognesi A, Polito L, Farini V, Bortolotti M, Tazzari PL, Ratta M, Ravaioli A, Horenstein AL, Stirpe F, Battelli MG, and Malavasi F
- Subjects
- Antibodies, Monoclonal pharmacology, Antineoplastic Agents, Phytogenic pharmacology, Cell Line, Tumor, Cell Separation, Drug Design, Humans, Immunotoxins pharmacology, In Vitro Techniques, N-Glycosyl Hydrolases pharmacology, Plant Proteins pharmacology, Protein Synthesis Inhibitors pharmacology, Ribosome Inactivating Proteins, Type 1, Saporins, ADP-ribosyl Cyclase 1 metabolism, Hematologic Neoplasms immunology, Hematologic Neoplasms therapy, Immunotoxins immunology
- Abstract
An anti-CD38 mAb (IB4) coupled to saporin-S6, a type 1 ribosome-inactivating protein (RIP), was designed for ex vivo or loco-regional therapeutical applications in myeloma and lymphoma. The ability of this immunotoxin to eliminate CD38+ cells was studied in vitro on selected CD38+ human cell lines (Raji, HBL6, L540 and CEM) and on CD38+ neoplastic cells from a Non Hodgkin Lymphoma (NHL) patient. HBL6, Raji and L540 cells resulted very sensitive to the IB4/saporin-S6 conjugate, concentrations as low as 100 pM of the immunotoxin completely inhibited protein synthesis. CD38+ neoplastic cells from the NHL patient were completely eliminated after treatment with immunotoxin at 10 nM concentration. CFU-c rescue by bone marrow precursors was maintained after exposure to the immunotoxin. These results indicate that IB4/saporin-S6 is endowed with strong and specific cytotoxic effects on selected CD38+ tumor cells lineages. Consequently, it is reasonable to propose a clinical use of the IB4/saporin-S6 for ex vivo purging of unwanted cells (e.g. depletion of contaminating neoplastic cells in aphereses obtained from G-CSF-treated patients) or for loco-regional therapies of CD38+ tumors.
- Published
- 2005