Serum cytokines were serially measured using a Luminex assay while splenocytes at termination were analyzed by ELISpot to determine T /T polarization of immune Fisetin response. Results: Daily oral doses of 0 and mg/kg of tamoxifen and letrozo respective resulted in a significant survival advantage over controls . A predominant T polarized immune response in vaccinated mice was seen with or without tamoxifen or letrozole treatments. In the L-BL 5 plus letrozole treatment gro statistically significant additive antitumor activity was observ whereas tamoxifen plus L-BL 5 was not significantly different . Downloaded from clincancerres.aacrjournals on March 9, Copyright American Association for Cancer Research Author Manuscript Published OnlineFirst on March 0. DOI: .CCR Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Conclusion:
The results of the present study demonstrate that hormonal therapy does not interfere with L-BL 5 induced predominant T respon and thebination of L-BL 5 with letrozole has additive antitumor activity in the MMT mouse model. Downloaded from TG-101348 936091-26-8 clincancerres.aacrjournals on March 9, Copyright American Association for Cancer Research Author Manuscript Published OnlineFirst on March 0. DOI: .CCR Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Breast cancer is one of the leading causes of cancer death in women and accounts for one-third of all cancer diagnoses worldwide . The majority of breast cancer patients will develop estrogen receptor positive tumors and will receive a hormonal agent during the course of their treatment. Unfortunate a subset of patients will develop hormone-independent and/or triple negative breast cancer .
For these patients with limited treatment options it is important to consider a new buy PF-562271 immunotherapy that targets a tumor associated antigen that is expressed on tumors irrespective of hormone status. MU or Muci glycoprotein is a TAA overexpressed in greater than 0 of human breast cancers . Although MU is a molecule physiologically expressed on a variety of mammalian cel its expression is significantly altered in tumorigenesis. Overall expression of MU increases on cancer cells and it is underglycosylated revealing variable number of tandem repeat regions on a peptide backbone. T cells specific for antigenic epitopes of MU that bind to HLA class I molecules have been identified and isolated from the blood and bone marrow of breast cancer and MDV3100 Androgen Receptor inhibitor myeloma patien making MU a potential target for a cellular immune response .
In additi the immunodominant peptides from the VNTR region are recognized by cytotoxic T-lymphocytes that are thought to destroy tumor cells expressing the underglycosylated form of MU . L-BL 5, a liposomal vacci consists of immunodominant peptides from the VNTR region of MU . This vaccine generates CTLs capable of destroying MU -expressing tumor cells and produces T polarized cytokine responses . L-BL 5 liposomal vaccine is in Phase III clinical development for non-small Downloaded from carbon dioxide clincancerres.aacrjournals on March 9, Copyright American Association for Cancer Research Author Manuscript Published OnlineFirst on March 0. DOI: .CCR Author manuscripts have been peer reviewed.