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.
Taylor
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DD
Department of Obstetrics and Gynecology, University of Louisville School of Medicine, Kentucky 40292.
Gerçel-Taylor
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C
Fowler
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WC
Weese
J L
JL
D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary / Q000628:therapy*; D000276:Adjuvants, Immunologic; D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D017024:Chemotherapy, Adjuvant; D004195:Disease Models, Animal; D005472:Fluorouracil / Q000627:therapeutic use*; D007167:Immunotherapy; D007978:Levamisole / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000628:therapy*; D016305:Thymopentin / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D007978:Levamisole; D016305:Thymopentin; D005472:Fluorouracil