In silico Analysis of Suitable Immunogenic WT۱ Epitopes in Iranian Population for Targeted Immunotherapies

Recognition of suitable epitopes to elicit cellular immunity against a specific antigen is a prerequisite of developing new targeted immunotherapies for cancer. Protein of Wilms' Tumor gene ۱ (WT۱), is a transcription factor and a tumor-associated antigen that is overexpressed in a wide range of cancers. Despite the growing interest in WT۱-redirected immunotherapies worldwide, there is no available data on proper epitopes matching Iranian population. Hence, in this study, we sought to identify potentially immunogenic WT۱ epitopes that can be presented on the most common human leukocyte antigen (HLA) alleles in Iranian people. Methods: Allele Frequency Net Database (AFND) and existing literature were reviewed to determine the most common class I HLA alleles in the Iranian population. The most prevalent allele in each locus were selected. The entire WT۱ protein sequence was obtained from the UniProt database and analyzed using the Immune Epitope Database (IEDB) T cell Epitope Prediction Tools, considering the selected HLA alleles. The epitopes were ranked using the NetMHCpan-۴.۱ algorithm, by calculating the eluted ligand (EL) scores. Finally, the RANKPEP algorithm was employed to predict potential peptide cleavage by proteases, which helps in the presentation of the peptides. Results: According to AFND and relevant literature, HLA-A*۰۲۰۱, HLA-B*۳۵۰۱ and HLA-C*۰۴۰۱ are the most common alleles in each locus of class I HLA in Iran. Based on EL scores, the top three epitopes for each allele are as follows: ALLPAVPSL, SLGEQQYSV and RMFPNAPYL for HLA-A*۰۲۰۱; TPYSSDNLY, FAPPGASAY, and VTFDGTPSY for HLA-B*۳۵۰۱; TFDGTPSY, FAPPGASAY and RMFPNAPYL for HLA-C*۰۴۰۱. Additionally, ALLPAVPSL, RMFPNAPYL, VTFDGTPSY, TFDGTPSY and FAPPGASAY were predicted by the RANKPEP algorithm to have cleavage sites for intracellular protease enzymes, suggesting a higher likelihood of effective peptide presentation. Conclusion: Using valid databases and through in silico analyses, we successfully identified potentially immunogenic epitopes that may be useful for developing WT۱-targeted immunotherapies for the Iranian population. Further research, however, is required to validate these predicted epitopes.

کلیدواژه ها:

Antigen Presentation ، Epitopes ، Immunotherapy ، Targeted Therapy ، Wilms Tumor Genes