In vitro anti-tumour activity of anti-CD80 and anti-CD86 immunotoxins containing type 1 ribosome-inactivating proteins.
Immunotoxins specific for the CD80 and CD86 antigens were prepared by linking three type 1 ribosome-inactivating proteins (RIPs), namely bouganin, gelonin and saporin-S6, to the monoclonal antibodies M24 (anti-CD80) and 1G10 (anti-CD86). These immunotoxins showed a specific cytotoxicity for the CD80/CD86-expressing cell lines Raji and L428. The immunotoxins inhibited protein synthesis by target cells with IC50s (concentration causing 50% inhibition) ranging from 0.25 to 192 pmol/l as RIPs. The anti-CD80 immunotoxins appeared 1-2 log more toxic for target cells than the anti-CD86 ones. Immunotoxins containing saporin and bouganin induced apoptosis of target cells. The toxicity for bone marrow haemopoietic progenitors of these conjugates was also evaluated. Bouganin and related immunotoxins at concentrations up to 100 nmol/l did not significantly affect the recovery of committed progenitors or of more primitive cells. The saporin-containing immunotoxins at concentrations >/= 1 nmol/l showed some toxicity on colony-forming unit cells (CFU-C). The expression of the CD80 and CD86 molecules is prevalently restricted to antigen-presenting cells and is also strong on Hodgkin and Reed-Sternberg cells in Hodgkin's disease. Present results suggest that immunotoxins targeting type 1 ribosome-inactivating proteins to these antigens could be considered and further studied for the therapy of Hodgkin's disease or other CD80/CD86-expressing tumours.
Bolognesi
A
A
Dipartimento di Patologia Sperimentale and Istituto di Ematologia e Oncologia medica 'L. & A. Seràgnoli', Università di Bologna, Bologna, Italy. bolo@alma.unibo.it
Polito
L
L
Tazzari
P L
PL
Lemoli
R M
RM
Lubelli
C
C
Fogli
M
M
Boon
L
L
de Boer
M
M
Stirpe
F
F
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D018122:B7-1 Antigen / Q000187:drug effects*; D051940:B7-2 Antigen; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D008562:Membrane Glycoproteins / Q000627:therapeutic use*; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000627:therapeutic use*; D011500:Protein Synthesis Inhibitors; D054790:Ribosome Inactivating Proteins, Type 2; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000970:Antineoplastic Agents; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D000922:Immunotoxins; D008562:Membrane Glycoproteins; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D054790:Ribosome Inactivating Proteins, Type 2; D009699:N-Glycosyl Hydrolases