Mouse lewis lung carcinoma and hepatoma ascites treatment by combination of liposome chemotherapy and non‐specific immunotherapy

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Abstract
Liposomes have been used as biological carriers of anti‐tumor drugs, and their potential use has been tested in mouse Lewis lung carcinoma and hepatoma ascites tumor models. Ara‐C3 given by the intraperitoneal i.p. route either at 35 mg/kg in a single dose or at 2.5 mg/kg/dose with 5 doses/day for 3 days had no effect on the average survival time of i.v. implanted LLC. However, the same single dose of Ara‐C encapsulated in positively charged MLV significantly improved the average survival time of LLC‐bearing mice. MTX was chosen as a test drug for the treatment of hepatoma ascites. Non‐encapsulated MTX given at either 3 or 30 mg/kg by the i.p. route had little effect on the average survival of i.p.‐implanted hepatoma ascites. However, MTX encapsulated in SUV at a 3 mg/kg dose by the i.p. route significantly improved the average survival time of tumor‐bearing mice. A combination of chemotherapy and non‐specific immunotherapy has also been tested with these 2 tumor models. Two non‐specific microbial immune stimulators, Bacillus Calmette Guérin (BCG) and Corynebacterium parvum (CP) were tested by both the i.v. and i.p. routes. A combination of BCG therapy with non‐encapsulated anti‐tumor drugs was not effective for either of the tumor models. A combination of BCG therapy with liposome therapy appeared to improve the average survival time of LLC‐bearing mice. In particular, BCG treatment by the i.p. route in combination with liposome therapy resulted in a 20% long‐term survival rate among treated mice. However, BCG therapy by either route in combination with SUV encapsulated MTX therapy had no effect on the average survival time of hepatoma ascites‐bearing mice. Immunostimulation with CP at a given dose appears to be superior to BCG therapy for both tumor models. In the treatment of LLC, injection of CP by either the i.v. or i.p. route appears to be equally effective in combination with liposome therapy. However, for the treatment of hepatoma ascites, CP was only effective by the i.p. route, in combination with liposome therapy.