An ineffective monoclonal antibody-ricin A chain conjugate is converted to a tumouricidal agent in vivo by subsequent systemic administration of ricin B chain.
An immunotoxin comprising a tumour-specific monoclonal antibody (11/160) coupled to ricin A chain, although inactive in in vitro cytotoxicity assays against HSNtc sarcoma target cells, was found to be capable of significant tumouricidal activity in syngeneic rats if potentiated by ricin B chain. The 11/160-ricin A, when bound to tumour cells prior to their inoculation, led to a slight inhibition of tumour growth s.c. compared with untreated sarcoma cells or those coated with antibody alone. However, all tumours in these groups developed progressively (69/69), whereas in those rats receiving 15 micrograms or 150 micrograms ricin B chain i.v. 5 min after tumour cell inoculation, the 'take rate' was reduced to 75% and 30% respectively, and significantly longer latent periods were evident for those tumours which did develop. Ricin B chain similarly inhibited, in a dose-dependent manner, the lung colonisation potential of 11/160-ricin A coated HSNtc cells. No effects were obtained if the B chain treatment followed inoculation of untreated or antibody-coated cells, suggesting that systemically administered B chain is capable of gaining access to and activating antibody-ricin A chain conjugates bound to the surface of syngeneic sarcoma cells in lung or subcutaneous sites. Tumour inhibition was obtained in some instances with intervals of up to 24 h between inoculation of conjugate-coated tumour cells and B chain. Experiments are in progress to determine if such potentiation may be feasible in a therapeutic rather than a prophylactic setting using this syngeneic solid tumour system.
D000818:Animals; D002460:Cell Line; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007167:Immunotherapy; D000922:Immunotoxins / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008297:Male; D010446:Peptide Fragments; D051381:Rats; D011919:Rats, Inbred Strains; D012276:Ricin
D000922:Immunotoxins; D010446:Peptide Fragments; D012276:Ricin