Purpose:In the present study, we examine the immunomodulatory effects and antitumor activity of tamoxifen and letrozole when combined with the human epithelial mucin (hMUC1) specific vaccine, L-BLP25, in the hMUC1-expressing mammary tumor (MMT) mouse model. Experimental Design:Dose-finding studies were conducted for both tamoxifen and letrozole. Letrozole and L-BLP25 combination studies used 69 MMT female mice assigned to five groups: untreated, cyclophosphamide + placebo, cyclophosphamide + L-BLP25, letrozole 0.8 mg/kg and cyclophosphamide + L-BLP25 + letrozole. Tamoxifen and L-BLP25 combination studies used 48 MMT female mice assigned to five treatment groups: untreated, cyclophosphamide + placebo, cyclophosphamide + L-BLP25, tamoxifen 50 mg/kg and cyclophosphamide + L-BLP25 + tamoxifen 50 mg/kg group. Mice were injected subcutaneously with L-BLP25 (10 µg) weekly for eight weeks. Serum cytokines were serially measured using a Luminex assay while splenocytes at termination were analyzed by ELISpot to determine Th1/Th2 polarization of immune response. Results:Daily oral doses of 50 and 0.8 mg/kg of tamoxifen and letrozole, respectively, resulted in a significant survival advantage over controls (p<0.05). A predominant Th1 polarized immune response in vaccinated mice was seen with or without tamoxifen or letrozole treatments. In the L-BLP25 plus letrozole treatment group, statistically significant (p<0.05) additive antitumor activity was observed, whereas tamoxifen plus L-BLP25 was not significantly different (p>0.05). Conclusions:The results of the present study demonstrate that hormonal therapy does not interfere with L-BLP25 induced predominant Th1 response, and the combination of L-BLP25 with letrozole has additive antitumor activity in the MMT mouse model.
- Received January 20, 2012.
- Revision received March 9, 2012.
- Accepted March 13, 2012.
- Copyright © 2012, American Association for Cancer Research.