Title:In silico Identification of MHC Displayed Tumor Associated Peptides in
Ovarian Cancer for Multi-Epitope Vaccine Construct
Volume: 24
Issue: 12
Author(s): Shivashish Dobhal, Kanchan Chauhan, Sachin Kumar, Sristy Shikha, Mukesh K. Jogi, Dinesh Kumar, Anuj Kumar, Varun K. Jaiswal and Pramod Kumar*
Affiliation:
- Division of Molecular Biology, Indian Council of Medical
Research (ICMR)-National Institute of Cancer Prevention and Research (NICPR), Noida, 201301, India
Keywords:
Ovarian cancer, immune checkpoint inhibition (ICI), tumor-associated antigens (TAAs), in silico evaluation, MUC16, epitopes.
Abstract:
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.
