L-BLP25 vaccine plus letrozole induces a T H1 immune response and has additive antitumor activity in MUC1-expressing mammary tumors in mice

Neelima R. Mehta, Gregory T. Wurz, Rebekah A. Burich, Brittany E. Greenberg, Stephen M Griffey, Audrey Gutierrez, Katie E. Bell, Jamie L. McCall, Michael Wolf, Michael DeGregorio

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9 Scopus citations

Abstract

Purpose: In this 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 + LBLP25 + letrozole. Tamoxifen and L-BLP25 combination studies used 48MMT 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 mg) weekly for 8 weeks. Serum cytokines were serially measured using a Luminex assay, whereas splenocytes at termination were analyzed by ELISpot to determine T-helper (T H)1/T H2 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). Conclusion: The results of this study show that hormonal therapy does not interfere with L-BLP25-induced predominant T H1 response, and the combination of L-BLP25 with letrozole has additive antitumor activity in the MMT mouse model.

Original languageEnglish (US)
Pages (from-to)2861-2871
Number of pages11
JournalClinical Cancer Research
Volume18
Issue number10
DOIs
StatePublished - May 15 2012

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Mehta, N. R., Wurz, G. T., Burich, R. A., Greenberg, B. E., Griffey, S. M., Gutierrez, A., Bell, K. E., McCall, J. L., Wolf, M., & DeGregorio, M. (2012). L-BLP25 vaccine plus letrozole induces a T H1 immune response and has additive antitumor activity in MUC1-expressing mammary tumors in mice. Clinical Cancer Research, 18(10), 2861-2871. https://doi.org/10.1158/1078-0432.CCR-12-0168