CD38 as a target of IB4 mAb carrying saporin-S6: design of an immunotoxin for ex vivo depletion of hematological CD38+ neoplasia.
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.
Bolognesi
A
A
Department of Experimental Pathology, University of Bologna, Italy. andrea.bolognesi@unibo.it
Polito
L
L
Farini
V
V
Bortolotti
M
M
Tazzari
P L
PL
Ratta
M
M
Ravaioli
A
A
Horenstein
A L
AL
Stirpe
F
F
Battelli
M G
MG
Malavasi
F
F
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D045744:Cell Line, Tumor; D002469:Cell Separation; D015195:Drug Design; D019337:Hematologic Neoplasms / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D000922:Immunotoxins / Q000276:immunology* / Q000494:pharmacology; D066298:In Vitro Techniques; D009699:N-Glycosyl Hydrolases / Q000494:pharmacology; D010940:Plant Proteins / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D051997:ADP-ribosyl Cyclase 1