Next Article in Journal
Turning on the Radio: Epigenetic Inhibitors as Potential Radiopriming Agents
Next Article in Special Issue
Mucin-Type O-Glycosylation in Gastric Carcinogenesis
Previous Article in Journal
Mechanistic and Structural Studies of Protein-Only RNase P Compared to Ribonucleoproteins Reveal the Two Faces of the Same Enzymatic Activity
Previous Article in Special Issue
A Bitter Sweet Symphony: Immune Responses to Altered O-glycan Epitopes in Cancer
Article Menu

Export Article

Open AccessArticle
Biomolecules 2016, 6(3), 31; doi:10.3390/biom6030031

Aberrant Glycosylation of Anchor-Optimized MUC1 Peptides Can Enhance Antigen Binding Affinity and Reverse Tolerance to Cytotoxic T Lymphocytes

1
Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic in Arizona, 13400 E. Shea Boulevard, Scottsdale, AZ 85259, USA
2
Department of Immunology, College of Medicine, Mayo Clinic in Arizona, 13400 E. Shea Boulevard, Scottsdale, AZ 85259, USA
3
Cancer Center Statistics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
4
Department of Surgery, Mayo Clinic in Arizona, Mayo Clinic Hospital, 5777 E. Mayo Boulevard, Phoenix, AZ 85054, USA
Present address: Department of Biology, University of North Carolina, Charlotte, NC 28223, USA.
*
Author to whom correspondence should be addressed.
Academic Editor: Franz-Georg Hanisch
Received: 30 April 2016 / Revised: 7 June 2016 / Accepted: 7 June 2016 / Published: 29 June 2016
(This article belongs to the Special Issue Cancer and Glycosylation)
View Full-Text   |   Download PDF [1908 KB, uploaded 29 June 2016]   |  

Abstract

Cancer vaccines have often failed to live up to their promise, although recent results with checkpoint inhibitors are reviving hopes that they will soon fulfill their promise. Although mutation-specific vaccines are under development, there is still high interest in an off-the-shelf vaccine to a ubiquitous antigen, such as MUC1, which is aberrantly expressed on most solid and many hematological tumors, including more than 90% of breast carcinomas. Clinical trials for MUC1 have shown variable success, likely because of immunological tolerance to a self-antigen and to poor immunogenicity of tandem repeat peptides. We hypothesized that MUC1 peptides could be optimized, relying on heteroclitic optimizations of potential anchor amino acids with and without tumor-specific glycosylation of the peptides. We have identified novel MUC1 class I peptides that bind to HLA-A*0201 molecules with significantly higher affinity and function than the native MUC1 peptides. These peptides elicited CTLs from normal donors, as well as breast cancer patients, which were highly effective in killing MUC1-expressing MCF-7 breast cancer cells. Each peptide elicited lytic responses in greater than 6/8 of normal individuals and 3/3 breast cancer patients. The CTLs generated against the glycosylated-anchor modified peptides cross reacted with the native MUC1 peptide, STAPPVHNV, suggesting these analog peptides may offer substantial improvement in the design of epitope-based vaccines. View Full-Text
Keywords: Tn antigen; vaccine; immunotherapy; CTL; breast cancer; Mucin1; heteroclitic antigen Tn antigen; vaccine; immunotherapy; CTL; breast cancer; Mucin1; heteroclitic antigen
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Pathangey, L.B.; Lakshminarayanan, V.; Suman, V.J.; Pockaj, B.A.; Mukherjee, P.; Gendler, S.J. Aberrant Glycosylation of Anchor-Optimized MUC1 Peptides Can Enhance Antigen Binding Affinity and Reverse Tolerance to Cytotoxic T Lymphocytes. Biomolecules 2016, 6, 31.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biomolecules EISSN 2218-273X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top