Indomethacin enhances anti-tumor efficacy of a MUC1 peptide vaccine against breast cancer in MUC1 transgenic mice.
In recent years, vaccines against tumor antigens have shown potential for combating invasive cancers, including primary tumors and metastatic lesions. This is particularly pertinent for breast cancer, which is the second-leading cause of cancer-related death in women. MUC1 is a glycoprotein that is...
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| Format: | Article |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0224309 |
| _version_ | 1818678564970561536 |
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| author | Jennifer M Curry Dahlia M Besmer Timothy K Erick Nury Steuerwald Lopamudra Das Roy Priyanka Grover Shanti Rao Sritama Nath Jacob W Ferrier Robert W Reid Pinku Mukherjee |
| author_facet | Jennifer M Curry Dahlia M Besmer Timothy K Erick Nury Steuerwald Lopamudra Das Roy Priyanka Grover Shanti Rao Sritama Nath Jacob W Ferrier Robert W Reid Pinku Mukherjee |
| author_sort | Jennifer M Curry |
| collection | DOAJ |
| description | In recent years, vaccines against tumor antigens have shown potential for combating invasive cancers, including primary tumors and metastatic lesions. This is particularly pertinent for breast cancer, which is the second-leading cause of cancer-related death in women. MUC1 is a glycoprotein that is normally expressed on glandular epithelium, but is overexpressed and under-glycosylated in most human cancers, including the majority of breast cancers. This under-glycosylation exposes the MUC1 protein core on the tumor-associated form of the protein. We have previously shown that a vaccine consisting of MUC1 core peptides stimulates a tumor-specific immune response. However, this immune response is dampened by the immunosuppressive microenvironment within breast tumors. Thus, in the present study, we investigated the effectiveness of MUC1 vaccination in combination with four different drugs that inhibit different components of the COX pathway: indomethacin (COX-1 and COX-2 inhibitor), celecoxib (COX-2 inhibitor), 1-methyl tryptophan (indoleamine 2,3 dioxygenase inhibitor), and AH6809 (prostaglandin E2 receptor antagonist). These treatment regimens were explored for the treatment of orthotopic MUC1-expressing breast tumors in mice transgenic for human MUC1. We found that the combination of vaccine and indomethacin resulted in a significant reduction in tumor burden. Indomethacin did not increase tumor-specific immune responses over vaccine alone, but rather appeared to reduce the proliferation and increase apoptosis of tumor cells, thus rendering them susceptible to immune cell killing. |
| first_indexed | 2024-12-17T09:17:17Z |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
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| last_indexed | 2024-12-17T09:17:17Z |
| publishDate | 2019-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-15f6f579b4ae4c04ac423dc647dfd3302022-12-21T21:54:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-011411e022430910.1371/journal.pone.0224309Indomethacin enhances anti-tumor efficacy of a MUC1 peptide vaccine against breast cancer in MUC1 transgenic mice.Jennifer M CurryDahlia M BesmerTimothy K ErickNury SteuerwaldLopamudra Das RoyPriyanka GroverShanti RaoSritama NathJacob W FerrierRobert W ReidPinku MukherjeeIn recent years, vaccines against tumor antigens have shown potential for combating invasive cancers, including primary tumors and metastatic lesions. This is particularly pertinent for breast cancer, which is the second-leading cause of cancer-related death in women. MUC1 is a glycoprotein that is normally expressed on glandular epithelium, but is overexpressed and under-glycosylated in most human cancers, including the majority of breast cancers. This under-glycosylation exposes the MUC1 protein core on the tumor-associated form of the protein. We have previously shown that a vaccine consisting of MUC1 core peptides stimulates a tumor-specific immune response. However, this immune response is dampened by the immunosuppressive microenvironment within breast tumors. Thus, in the present study, we investigated the effectiveness of MUC1 vaccination in combination with four different drugs that inhibit different components of the COX pathway: indomethacin (COX-1 and COX-2 inhibitor), celecoxib (COX-2 inhibitor), 1-methyl tryptophan (indoleamine 2,3 dioxygenase inhibitor), and AH6809 (prostaglandin E2 receptor antagonist). These treatment regimens were explored for the treatment of orthotopic MUC1-expressing breast tumors in mice transgenic for human MUC1. We found that the combination of vaccine and indomethacin resulted in a significant reduction in tumor burden. Indomethacin did not increase tumor-specific immune responses over vaccine alone, but rather appeared to reduce the proliferation and increase apoptosis of tumor cells, thus rendering them susceptible to immune cell killing.https://doi.org/10.1371/journal.pone.0224309 |
| spellingShingle | Jennifer M Curry Dahlia M Besmer Timothy K Erick Nury Steuerwald Lopamudra Das Roy Priyanka Grover Shanti Rao Sritama Nath Jacob W Ferrier Robert W Reid Pinku Mukherjee Indomethacin enhances anti-tumor efficacy of a MUC1 peptide vaccine against breast cancer in MUC1 transgenic mice. PLoS ONE |
| title | Indomethacin enhances anti-tumor efficacy of a MUC1 peptide vaccine against breast cancer in MUC1 transgenic mice. |
| title_full | Indomethacin enhances anti-tumor efficacy of a MUC1 peptide vaccine against breast cancer in MUC1 transgenic mice. |
| title_fullStr | Indomethacin enhances anti-tumor efficacy of a MUC1 peptide vaccine against breast cancer in MUC1 transgenic mice. |
| title_full_unstemmed | Indomethacin enhances anti-tumor efficacy of a MUC1 peptide vaccine against breast cancer in MUC1 transgenic mice. |
| title_short | Indomethacin enhances anti-tumor efficacy of a MUC1 peptide vaccine against breast cancer in MUC1 transgenic mice. |
| title_sort | indomethacin enhances anti tumor efficacy of a muc1 peptide vaccine against breast cancer in muc1 transgenic mice |
| url | https://doi.org/10.1371/journal.pone.0224309 |
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