Identification of immunogenic MAGED4B peptides for vaccine development in oral cancer immunotherapy
Kue Peng Lim1, Nicole Ai Leng Chun, Chai Phei Gan
1a Oral Cancer Research Team; Cancer Research Initiatives Foundation (CARIF) ; Subang Jaya , Selangor , Malaysia.
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.
Insights
Researchers identified MAGED4B peptides that trigger anti-tumor immune responses. These peptides show promise as potential vaccine candidates for oral squamous cell carcinoma (OSCC) treatment.
Area of Science:
- Immunology
- Oncology
- Vaccine Development
Background:
- Therapeutic peptide vaccines are increasingly important due to rising tumor-associated antigens.
- MAGED4B, a melanoma antigen, is overexpressed in oral squamous cell carcinoma (OSCC), driving tumor growth and metastasis.
Purpose of the Study:
- To identify MAGED4B-derived peptides that can elicit an anti-tumor immune response for OSCC treatment.
- To evaluate the immunogenicity and efficacy of these peptides in preclinical models.
Main Methods:
- Identification of 9 short peptides from MAGED4B with binding affinity to common Asian HLA subtypes (HLA-A2, A11, A24).
- Assessment of peptide binding to MHC-Class I molecules.
- Ex-vivo stimulation of peripheral blood mononuclear cells (PBMCs) from OSCC patients to measure IFN-gamma and Granzyme-B production.
- Evaluation of T-cell cytotoxic activity against OSCC cell lines after stimulation with peptide-pulsed dendritic cells.
Main Results:
- The identified MAGED4B peptides demonstrated good binding affinity to MHC-Class I molecules.
- Peptides stimulated significant IFN-gamma and Granzyme-B production in OSCC patient blood samples, indicating immunogenicity.
- T cells activated by these peptides exhibited enhanced cytotoxic activity against MAGED4B-expressing OSCC cell lines.
Conclusions:
- MAGED4B-derived peptides are immunogenic and can induce anti-tumor immune responses.
- These peptides represent promising candidates for the development of novel peptide vaccines against oral squamous cell carcinoma.
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