From Personalized to Multi-Patient: Shared Sequences of Female Reproductive System Cancer Neoepitopes with Other Cancer Neoepitopes for Refurbished Vaccine Candidates (Data Mining-Based Study)

Abstract

Objective: We aim to identify female reproductive system cancers' neoepitopes that can be used to develop personalized cancer vaccines with multi-patient applicability based on shared sequences among other cancer neoepitopes. Material and Methods: Immune Epitope Database (IEDB)-deposited cancer neoepitopes were inspected for shared pentapeptide sequences within linear neoepitopes, based on user-defined cutoffs, and were used to identify compatible human leukocyte antigen (HLA)-types. Shared pentapeptide sequences binding to the same HLA alleles were further selected and screened against the sequences of epitopes linked to autoimmune diseases deposited at IEDB to identify any potential for initiating a similar autoimmune response through cross-reaction. To support the possibility of cross-reactivity, the identified autoimmune disease-associated epitopes were back-predicted for their binding affinities to the same alleles as those of the neoepitopes of interest. Results: Gapless sequence alignment-based clustering of neoepitopes revealed that the group with the highest number of neoepitopes involved three female reproductive system cancer neoepitopes; two endometrial and one ovarian. Two other groups contained ovarian cancer-related neoepitopes. RAS-derived neoepitopes had the widest coverage among all identified shared neoepitopes across multiple cancer types, including endometrial cancer, and highest variation of HLA-alleles. HLA-alleles binding to endometrial and ovarian cancer neoepitopes were among the most prevalent alleles. Patients with neoepitopes from endometrial and ovarian cancers, who are also HLA-A*11:01 and HLA-B*07:02 carriers, respectively, may benefit from vaccines targeting the same sequence-sharing neoepitopes, with follow-up suggested for autoimmune response. Conclusion: Results suggest broader applicability of personalized cancer vaccines in patients having identical tumor-specific mutations and compatible HLA-types, including those with ovarian and endometrial cancer.