Immunological effects of native and polyethylene glycol-modified asparaginases from Vibrio succinogenes and Escherichia coli in normal and tumour-bearing mice.
The immunosuppressive effects of polyethylene glycol-modified asparaginases from Vibrio succinogenes (PEG-asparaginase VS) and Escherichia coli (PEG-asparaginase EC) have been investigated in mice. Measurements of the mitogen-induced blastogenic responses of splenocytes, harvested 5 days after in vivo administration of the PEG-enzymes, show that PEG-asparaginase VS is not immunosuppressive, whereas PEG-asparaginase EC does cause immunosuppression. Both enzymes cause the spleen to be smaller than the control mice. In mice carrying the L5178Y tumour and its associated LDH-elevating virus, which causes the circulation life of asparaginase VS to be comparable to that of PEG-asparaginase VS, tumour regression and its attendant immunological changes are identical in animals treated with either the native or the modified enzyme. The data presented in this paper, along with independent immunological evidence presented by other workers strongly suggest that PEG-asparaginase VS may be the enzyme of choice for clinical use.
D000818:Animals; D001215:Asparaginase / Q000494:pharmacology* / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D004926:Escherichia coli / Q000201:enzymology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology*; D009929:Organ Size / Q000187:drug effects; D011092:Polyethylene Glycols / Q000494:pharmacology*; D013154:Spleen / Q000033:anatomy & histology; D014733:Vibrio / Q000201:enzymology
D007166:Immunosuppressive Agents; D011092:Polyethylene Glycols; D001215:Asparaginase