Nibeyro Guadalupe, Flesia Rocío, Orschanski Daniela, Nava Agustín, Baronetto Verónica, Fernández Elmer A
ScireLab @ Fundación para el Progreso de la Medicina, Córdoba, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina.
Methods Mol Biol. 2025;2930:139-156. doi: 10.1007/978-1-0716-4558-1_11.
The identification of tumor-specific neoantigen (TSN) immunogenicity is crucial to develop peptide/mRNA based antitumoral vaccines and/or adoptive T cell immunotherapies. In silico immunogenicity prediction of candidate peptides is crucial to speed up the prioritization of such peptides for experimental validation. Up to now, several methods were proposed as TSN immunogenicity predictors, but there are still several drawbacks in both performance and comprehensive performance evaluation, mainly due to the absence of well documented and adequate TSN databases.The Immunogenic Tumor-Specific Neoantigen database (ITSNdb) is a tool developed to fairly benchmark immunogenicity predictors intended to be used over tumoral neopeptides. The proposed ITSNdb enables the analysis of immunogenicity without the interference of other variables such as binding affinity or peptide processing, as they were considered into the inclusion criteria for the curation of neoantigens. ITSNdb, together with a dataset emulating a true patient neoantigens scenario, as a validation strategy for prioritization, and a list of neopeptides predicted to bind to major histocompatibility complex I (MHC-I) from immune checkpoint blockade immunotherapy (ICB) cohorts, along with their associated patient outcomes, is available to evaluate tumor neoantigen burden as a biomarker for ICB response (accessible at https://github.com/elmerfer/ITSNdb ).
肿瘤特异性新抗原（TSN）免疫原性的鉴定对于开发基于肽/信使核糖核酸的抗肿瘤疫苗和/或过继性T细胞免疫疗法至关重要。候选肽的计算机免疫原性预测对于加快此类肽用于实验验证的优先级排序至关重要。到目前为止，已经提出了几种方法作为TSN免疫原性预测指标，但在性能和综合性能评估方面仍存在一些缺点，主要是由于缺乏记录完善且足够的TSN数据库。免疫原性肿瘤特异性新抗原数据库（ITSNdb）是一种开发用于公平地对旨在用于肿瘤新肽的免疫原性预测指标进行基准测试的工具。所提出的ITSNdb能够在不受到其他变量（如结合亲和力或肽加工）干扰的情况下分析免疫原性，因为这些变量已被纳入新抗原编目的纳入标准中。ITSNdb连同模拟真实患者新抗原情况的数据集（作为优先级排序的验证策略）以及从免疫检查点阻断免疫疗法（ICB）队列中预测与主要组织相容性复合体I（MHC-I）结合的新肽列表及其相关患者结局，可用于评估肿瘤新抗原负担作为ICB反应的生物标志物（可在https://github.com/elmerfer/ITSNdb上获取）。
