Immunotherapy of L1210 leukemia using neuraminidase-modified plasma membranes combined with chemotherapy.
Purified L1210 plasma membranes treated with Vibrio cholerae neuraminidase (VCN) were used for active immunotherapy of L1210 tumors in DBA/2J mice. Immunotherapy with VCN-treated membranes was effective only when combined with 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU). Successful therapy was a function of the dose of MeCCNU, the dose of VCN-treated membranes, and the time after MeCCNU treatment when VCN-treated membranes were administered. Optimum conditions for treating animals with tumors initiated with 10(4) cells were MeCCNU (20/kg) given 3 days after tumor inoculation and 0.25 mg VCN-treated membranes given 1 day after chemotherapy. Control membranes, not treated with VCN, that were administered 1 day after MeCCNU were ineffective; when given 4 days after chemotherapy, the caused accelerated mortality, suggesting immunological enhancement of tumor growth. Our results indicate that VCN-treated plasma membranes can be used for active immunotherapy of established tumors and underscore the importance of carefully designing immunotherapy protocols to achieve optimum desirable effects.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002462:Cell Membrane / Q000276:immunology; D005260:Female; D007167:Immunotherapy; D007939:Leukemia L1210 / Q000628:therapy* / Q000648:ultrastructure; D051379:Mice; D009439:Neuraminidase / Q000378:metabolism; D009607:Nitrosourea Compounds / Q000627:therapeutic use*; D012673:Semustine / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D012673:Semustine; D009439:Neuraminidase