Enhancement of antitumor effects of combined chemoimmunotherapy

The spontaneously metastatic murine pancreatic tumor, PAN 2, was used to evaluate established regimens of combined chemoimmunotherapy with 5-fluorouracil (5-FU) and levamisole and new protocols based on the immunomodulator, thymopoietin pentapeptide (TP-5). The combination of 5-FU and levamisole reduced the final tumor size by 32% and the mean number of lung metastases by 71%. Based on flow cytometric analysis, the combination treatment increased the percent of helper/inducer (CD4+) lymphocytes and reduced the number of effector (suppressor/cytotoxic) lymphocytes (CD8+). A second combination using 5-FU and TP-5 produced a reduction in tumor growth rate of 52%, with an 88% suppression of lung metastases with TP-5/5-FU (vs. levamisole/5-FU) treatment. The TP-5 treatment also increased splenic T-lymphocyte responsiveness to nonspecific mitogens by 2.3-fold. These results suggest a correlation between enhanced T-lymphocyte functional parameters and reduced tumor growth and metastatic spread produced by these combination therapies. Since TP-5 has been demonstrated to be a superior immunomodulator compared to levamisole, the greater therapeutic effect of TP-5 vs. levamisole further supports the postulated role of immunopotentiation in the success of combined chemoimmunotherapy.