Effect of localization of L-asparaginase as the concanavalin A conjugate on anti-tumor activity.
A method potentially capable of enhancing the effectiveness of therapeutic enzymes such as L-asparaginase was investigated. The method was suggested by the following properties that have been observed for lectins injected into tissues: (1) six lectins with differing specificities were retained near the site of injection in the feet of mice 10 to 100 times longer than several non-lectin proteins. Prolonged retention of 125I-labelled concanavalin A was also observed in other normal and malignant mouse tissues. (2) The retention of 125I-labelled concanavalin A was not affected by prior immunization against concanavalin A. (3) Electrophoresis of tissue extracts on sodium dodecyl sulfate-poly-acrylamide gels followed by radioautography indicated that the 125I-labelled concanavalin A retained in the tissue remained as intact in form as prior to injection. Since the therapeutic efficacy of many enzymes may be enhanced by localization at the intended site of action, in principle it should be possible to enhance the effectiveness of therapeutic enzymes by combining the tissue-localizing properties of a lectin with therapeutic effectiveness of the enzyme. A conjugate of E. coli L-asparaginase and concanavalin A has been prepared by covalent cross-linking with glutaraldehyde and has been shown to be retained in mouse tissue 90 times longer than the free enzyme. However, it is completely ineffective in the treatment of the L-asparaginase-sensitive lymphosarcoma 6C3HED in C3H/HeJ mice. The ineffectiveness of the conjugated enzyme may be associated with the interiorization of the conjugate by the cells of the tumor.
D000818:Animals; D001215:Asparaginase / Q000378:metabolism / Q000627:therapeutic use*; D002460:Cell Line; D003208:Concanavalin A / Q000378:metabolism* / Q000627:therapeutic use; D004591:Electrophoresis, Polyacrylamide Gel; D007114:Immunization; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology; D012710:Serum Albumin, Bovine
D003208:Concanavalin A; D012710:Serum Albumin, Bovine; D001215:Asparaginase