Format

Send to

Choose Destination
PLoS One. 2019 Nov 6;14(11):e0224309. doi: 10.1371/journal.pone.0224309. eCollection 2019.

Indomethacin enhances anti-tumor efficacy of a MUC1 peptide vaccine against breast cancer in MUC1 transgenic mice.

Author information

1
Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, United States of America.
2
Molecular Biology and Genomics Laboratory, Carolinas Medical Center, Charlotte, NC, United States of America.
3
Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, United States of America.
4
OncoTAb, Inc., Charlotte, NC, United States of America.

Abstract

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.

Conflict of interest statement

Pinku Mukherjee is the founder and Chief Scientific Officer (CSO) of OncoTAb, Inc., a startup company that owns patents and rights to the TAB004 antibody and markets the TAB004-based ELISA as a Laboratory Developed Test under the commercial name AgkuraTM Personal Score. OncoTAb, Inc. provided support in the form of salary for Pinku Mukherjee, but did not have any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This commercial affiliation does not alter our adherence to PLOS One policies on sharing data and materials. Other authors declare no financial interests.

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center