Effect of the thymic factor, thymostimulin (TP-1), on the survival rate of tumor-Bearing mice

The effect of treatment with the thymic factor thymostimulin (TP-1) on the survival rate of tumor-bearing mice was studied, using C57BL/6 mice inoculated with 1 Χ 10⁵ Lewis lung carcinoma (3LL) cells. TP-1 given from inoculation day (4 mg/ kg, twice weekly) caused a delay in the appearance of primary tumor [14.4 ± 1.1 (S.E.) days in control; 18.5 ± 1.4 days in TP-1-treated animals; p < 0.05], without changing ultimate survival rate. When primary tumor was resected, the incidence of fatal lung metastasis increased as a function of tumor size on resection day. TP-1 given after resection (same dose schedule) significantly increased survival rate as compared to resection only, provided that resected tumor diameter was <1.7 mm. The combination of TP-1 and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; single i.p. injection, 50 mg/kg) was effective in either resected or nonresected primary tumor. Without resection, TP-1 with CCNU cured (more than 6 months free of tumor; untreated animals died within 30 to 44 days) 55% of the animals, as compared to 23% cured by CCNU alone (p < 0.01). With resection animal cure rates were: resection (resected tumor diameter, 0.7 to 1.7 mm) alone, 42% cured; resection with CCNU, 47% cured; resection with TP-1, 70% cured; resection with CCNU and TP-1, 100% cured (last two groups significantly different from resection only). The results indicate a profound effect of TP-1 in prolonging life and increasing cure rate of tumor-bearing mice. This effect was manifested when tumor load was small and was apparently more pronounced on metastatic than on primary tumor.