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Immunotherapy of L1210 Leukemia Using Neuraminidase-modified Plasma Membranes Combined with Chemotherapy¹

Life Sciences Division, SRI International, Menlo Park, California 94025

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 10⁴ cells were MeCCNU (20 mg/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, they 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.

¹ This work was supported by Contract NO1-CB-64053 from the National Cancer Institute.

Received 12/ 3/80. Accepted 5/ 7/81.