title: L-BLP25 vaccine plus letrozole induces a TH1 immune response and has additive antitumor activity in MUC1-expressing mammary tumors in mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 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(H)2 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 T(H)1-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 this study show that hormonal therapy does not interfere with L-BLP25-induced predominant T(H)1 response, and the combination of L-BLP25 with letrozole has additive antitumor activity in the MMT mouse model.
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, University of California, Davis, Sacramento, California 95817, USA.
authors.forename: Neelima R
authors.initials: NR
authors.lastname: Mehta
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wurz
authors.forename: Rebekah A
authors.initials: RA
authors.lastname: Burich
authors.forename: Brittany E
authors.initials: BE
authors.lastname: Greenberg
authors.forename: Stephen
authors.initials: S
authors.lastname: Griffey
authors.forename: Audrey
authors.initials: A
authors.lastname: Gutierrez
authors.forename: Katie E
authors.initials: KE
authors.lastname: Bell
authors.forename: Jamie L
authors.initials: JL
authors.lastname: McCall
authors.forename: Michael
authors.initials: M
authors.lastname: Wolf
authors.forename: Michael
authors.initials: M
authors.lastname: DeGregorio
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D047072:Aromatase Inhibitors; D019496:Cancer Vaccines / Q000494:pharmacology / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D004958:Estradiol / Q000008:administration & dosage; D004965:Estrogen Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D000077289:Letrozole; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy*; D008562:Membrane Glycoproteins / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D018396:Mucin-1 / Q000096:biosynthesis*; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use; D018417:Th1 Cells / Q000276:immunology; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D019496:Cancer Vaccines; D004965:Estrogen Antagonists; C518273:L-BLP25; D008562:Membrane Glycoproteins; D018396:Mucin-1; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D018664:Interleukin-12; D004958:Estradiol; D000077289:Letrozole; D007371:Interferon-gamma; D003520:Cyclophosphamide