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In silico Identification of MHC Displayed Tumor Associated Peptides in Ovarian Cancer for Multi-Epitope Vaccine
Shivashish Dobhal1, Kanchan Chauhan1, Sachin Kumar1
1Amity Institute of Biotechnology, Amity University, Noida, India.
Background:
Recognizing the potential of the immune system, immunotherapies have brought about a revolution in the treatment of cancer. Low tumour mutational burden and strong immunosuppression in the peritoneal tumor microenvironment (TME) lead to poor outcomes of immune checkpoint inhibition (ICI) and CART cell therapy in ovarian cancer. Alternative immunotherapeutic strategies are of utmost importance to achieve sound clinical success.
Introduction:
The development of peptide vaccines based on tumor-associated antigens (TAAs) for ovarian cancer cells can be a potential target to provoke an anti-tumor immune response and subsequent clearance of tumour cells. The purpose of this in silico study was to find potential epitopes for a multi-epitope vaccine construct using the immunopeptidomics landscape of ovarian carcinoma.
Methods:
The four TAAs (MUC16, IDO1, FOLR1, and DDX5) were selected for potential epitopes prediction. The epitopes for B-cells, helper T-lymphocytes (HTL), and Cytotoxic Tlymphocytes (CTL) were predicted on the basis of antigenic, allergenic, and toxic properties. These epitopes were combined with suitable linkers and an adjuvant to form a multi-epitope construct.
Results:
Four HTLs, 13 CTLs, and 6 potential B-cell epitopes were selected from the predicted epitope. The designed multi-epitope construct was potentially immunogenic, non-toxic, and non-allergenic. Physicochemical properties and higher-order structural analyses of the final construct revealed a potential vaccine candidate.
Conclusion:
The designed vaccine construct has the potential to trigger both humoral and cellular immune responses and may be employed as a therapeutic immunization candidate for ovarian malignancies. However, further in vitro and animal experimentation is required to establish the efficacy of the vaccine candidate.
Insights
This study designed a novel multi-epitope vaccine construct for ovarian cancer by identifying potential tumor-associated antigen epitopes. The vaccine shows promise for triggering immune responses against ovarian cancer cells.
Area of Science:
- Oncology
- Immunology
- Vaccine Development
Background:
- Ovarian cancer immunotherapy faces challenges due to a suppressive tumor microenvironment.
- Existing treatments like immune checkpoint inhibition (ICI) and CAR T-cell therapy show limited efficacy.
- Novel immunotherapeutic strategies are crucial for improving clinical outcomes in ovarian cancer.
Purpose of the Study:
- To identify potential epitopes from tumor-associated antigens (TAAs) for ovarian cancer.
- To design a multi-epitope vaccine construct using immunopeptidomics data.
- To evaluate the immunogenic, non-toxic, and non-allergenic properties of the designed vaccine.
Main Methods:
- Selected four TAAs (MUC16, IDO1, FOLR1, DDX5) for epitope prediction.
- Predicted B-cell, helper T-lymphocyte (HTL), and cytotoxic T-lymphocyte (CTL) epitopes based on antigenic, allergenic, and toxic properties.
- Constructed a multi-epitope vaccine by combining selected epitopes with linkers and an adjuvant.
Main Results:
- Identified four HTL, 13 CTL, and six B-cell epitopes.
- The designed multi-epitope construct demonstrated potential immunogenicity.
- The vaccine candidate was predicted to be non-toxic and non-allergenic.
Conclusions:
- The developed vaccine construct can potentially elicit both humoral and cellular immune responses.
- This multi-epitope vaccine is a promising candidate for therapeutic immunization against ovarian cancer.
- Further in vitro and in vivo studies are necessary to validate the vaccine's efficacy.
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