Mapping the antigenic landscape of Multiple Myeloma to inform the development of precision cancer immunotherapies

本项目旨在利用来自MM患者的RNAseq、全外显子组和全基因组测序(WES和WGS)数据，从常见的融合事件/序列中预测新抗原，并在自体T细胞的共培养试验中测试推定的多肽，从而为靶向融合衍生的新抗原治疗MM提供原则性证据。为此，我们将追求以下目标：1.确定共享融合事件在患者中的分布，以创建潜在的个人/共享肿瘤抗原的全面图谱；2.验证MM和SMM患者中是否存在新抗原反应性T细胞，表征其表型并验证其细胞毒能力；3.提供新抗原反应性T细胞扩增和活性的概念证据(PoC)，对潜在的临床开发具有重要意义。该项目是对多发性骨髓瘤新抗原的首次全面研究，有可能导致发现治疗多发性骨髓瘤的新靶点。根据这个项目，这些新的抗原可以用来开发现成的基于T细胞疗法的治疗和/或SMM患者的预防性疫苗。与开发基于新抗原的T细胞疗法的领先公司Achilles的合作，确保了明确的翻译结果。

This project aims to use RNASeq, whole exome and whole genome sequencing (WES and WGS) data fromMM patients to predict neoantigens from common fusion events/sequences and test putative peptides in co-culture assays of autologous T cells to provide proof of principle to target fusion-derived neoantigensfor MM treatment.To achieve this, we will pursue the following objectives:1. Identify distribution of shared fusion events amongst patients to create a comprehensive map ofpotential personal/shared tumour neoantigens;2. Validate presence of neoantigen-reactive T cells in patients with MM and SMM, characterise themphenotypically and validate their cytotoxic capability;3. Provide proof of concept (PoC) of expansion and activity of neoantigen-reactive T cells forpotential clinical development.Importance. This project is the first comprehensive study of MM neoantigens, potentially leading to thediscovery of new targets for MM treatment. Following this project, these neoantigens could be used forthe development of off the shelf T cell therapy-based treatments and/or prophylactic vaccines for patientswith SMM. The collaboration with Achilles, a leading company developing neoantigen-based T celltherapies, guarantees a clear translational outcome.