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

绘制多发性骨髓瘤的抗原图谱，为精准癌症免疫疗法的发展提供信息

• 批准号: 2726319
• 金额: --
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2726319
• 关键词: Mapping; antigenic; landscape; Multiple; Myeloma

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.

该项目旨在利用来自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细胞共培养试验中测试推定的肽，为靶向融合衍生的新抗原治疗MM提供原理证明。为此，我们将努力实现以下目标：确定患者之间共享融合事件的分布，以创建潜在的个人/共享肿瘤新抗原的综合地图；2 .验证MM和SMM患者中存在新抗原反应性T细胞，表征其表型并验证其细胞毒性能力；为潜在的临床发展提供新抗原反应性T细胞扩增和活性的概念证明。该项目是第一个对MM新抗原的全面研究，可能会导致MM治疗新靶点的发现。在这个项目之后，这些新抗原可用于开发现成的基于T细胞疗法的治疗和/或SMM患者的预防性疫苗。与阿基里斯的合作，一家领先的公司开发基于新抗原的T细胞疗法，保证了一个明确的转化结果。