Abstract
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. 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. 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). 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.
Highlights
Breast cancer is one of the leading causes of cancer death in women and accounts for one third of all cancer diagnoses worldwide [1]
We examine the immunomodulatory effects and antitumor activity of L-BLP25 when combined with tamoxifen or letrozole in the hMUC1-expressing mammary tumor mouse model
mammary tumor (MMT) tumors respond to selective ER modulators (SERM)/AI treatment To determine the most effective doses of tamoxifen and letrozole in the MMT mouse model, we conducted a series of dose-finding studies
Summary
Breast cancer is one of the leading causes of cancer death in women and accounts for one third of all cancer diagnoses worldwide [1]. The majority of patients with breast cancer will develop estrogen receptor (ER)-positive tumors and will receive a hormonal agent during the course of their treatment. NeuÀ, progesterone receptor (PR)À] breast cancer [2] For these patients with limited treatment options, it is important to consider a new immunotherapy that targets a tumorassociated antigen (TAA) that is expressed on tumors irrespective of hormone status. Overall expression of MUC1 increases on cancer cells and it is underglycosylated revealing variable number of tandem repeat regions (VNTR) on a peptide backbone. The immunodominant peptides from the VNTR region are recognized by CTLs that are thought to destroy tumor cells expressing the underglycosylated form of MUC1 [11,12,13,14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
