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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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

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letrozole
Vaccines
Tamoxifen
Breast Neoplasms
Cyclophosphamide
Placebos
L-BLP25
Mucins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

L-BLP25 vaccine plus letrozole induces a T H1 immune response and has additive antitumor activity in MUC1-expressing mammary tumors in mice. / Mehta, Neelima R.; Wurz, Gregory T.; Burich, Rebekah A.; Greenberg, Brittany E.; Griffey, Stephen M; Gutierrez, Audrey; Bell, Katie E.; McCall, Jamie L.; Wolf, Michael; DeGregorio, Michael.

In: Clinical Cancer Research, Vol. 18, No. 10, 15.05.2012, p. 2861-2871.

Research output: Contribution to journalArticle

Mehta, NR, Wurz, GT, Burich, RA, Greenberg, BE, Griffey, SM, Gutierrez, A, Bell, KE, McCall, JL, 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, vol. 18, no. 10, pp. 2861-2871. https://doi.org/10.1158/1078-0432.CCR-12-0168
Mehta, Neelima R. ; Wurz, Gregory T. ; Burich, Rebekah A. ; Greenberg, Brittany E. ; Griffey, Stephen M ; Gutierrez, Audrey ; Bell, Katie E. ; McCall, Jamie L. ; Wolf, Michael ; DeGregorio, Michael. / L-BLP25 vaccine plus letrozole induces a T H1 immune response and has additive antitumor activity in MUC1-expressing mammary tumors in mice. In: Clinical Cancer Research. 2012 ; Vol. 18, No. 10. pp. 2861-2871.
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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.",
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T1 - L-BLP25 vaccine plus letrozole induces a T H1 immune response and has additive antitumor activity in MUC1-expressing mammary tumors in mice

AU - Mehta, Neelima R.

AU - Wurz, Gregory T.

AU - Burich, Rebekah A.

AU - Greenberg, Brittany E.

AU - Griffey, Stephen M

AU - Gutierrez, Audrey

AU - Bell, Katie E.

AU - McCall, Jamie L.

AU - Wolf, Michael

AU - DeGregorio, Michael

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N2 - 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.

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