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 linki ng three type 1 ribosome-inactivating proteins (RIPs), namely bouganin, gel onin 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 prote in synthesis by target cells with IC(50)s (concentration causing 50% inhibi tion) ranging from 0.25 to 192 pmol/l as RIPs. The anti-CD80 immunotoxins a ppeared 1-2 log more toxic for target cells than the anti-CD86 ones, Immuno toxins containing saporin and bouganin induced apoptosis of target cells. T he toxicity for bone marrow haemopoietic progenitors of these conjugates wa s also evaluated. Bouganin and related immunotoxins at concentrations up to 100 nmol/l did not significantly affect the recovery of committed progenit ors or of more primitive cells. The saporin-containing immunotoxins at conc entrations greater than or equal to 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 sug gest that immunotoxins targeting type 1 ribosome-inactivating proteins to t hese antigens could be considered and further studied for the therapy of Ho dgkin's disease or other CD80/CD86-expressing tumours.