Identification of immunogenic MAGED4B peptides for vaccine development in oral cancer immunotherapy

Abstract

The ever-increasing number of tumor-associated antigens has provided a major stimulus for the development of therapeutic peptides vaccines. Tumor-associated peptides can induce high immune response rates and have been developed as vaccines for several types of solid tumors, and many are at various stages of clinical testing. MAGED4B, a melanoma antigen, is overexpressed in oral squamous cell carcinoma (OSCC) and this expression promotes proliferation and cell migration. In this study, we have identified 9 short peptides derived from MAGED4B protein that are restricted in binding to the HLA subtypes common in the Asian population (HLA-A2, A11, and A24). The peptides had good binding affinity with the MHC-Class I molecules and stimulated ex-vivo IFN-gamma and Granzyme-B production in blood samples from OSCC patients, suggesting that they are immunogenic. Further, T cells stimulated with peptide-pulsed dendritic cells showed enhanced T-cell cytotoxic activity against MAGED4B-overexpressing OSCC cell lines. In summary, we have identified MAGED4B peptides that induce anti-tumor immune responses advocating that they could be further developed as vaccine candidates for the treatment of OSCC.

Keywords:

• immune system
• immunotherapy
• MAGED4B
• oral cancer
• peptide vaccine

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank our collaborating partners in Oral Cancer Research and Coordinating Center, University Malaya (OCRCC) in particular the Ministry Of Health Malaysia for collection of tissue and data under the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS).

Funding

This study was funded by the Ministry of Science, Technology and Innovation (MOSTI) of Malaysia (e-Science Fund, 02–04–03-SF0011) and other sponsors of the Cancer Research Initiatives Foundation (CARIF). CARIF is a non-profit research organization. We are committed to an understanding of cancer prevention, diagnosis and treatment through a fundamental research program.