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通过高分辨率质谱和新算法预测快速直接发现功能性肿瘤特异性新抗原

英文原题:Rapid and direct discovery of functional tumor specific neoantigens by high resolution mass spectrometry and novel algorithm prediction.

PubMed 2025/05/12(内容时间) Cell Insight Q1 · IF 6.4(JCR 2025)

研究概要

尽管免疫细胞疗法已经改变了癌症治疗格局,但与NHL和MM等血液系统恶性肿瘤相比,在实体瘤中取得同等成功仍然是一项重大挑战。

中文摘要

尽管免疫细胞疗法已经改变了癌症治疗格局,但与NHL和MM等血液系统恶性肿瘤相比,在实体瘤中取得同等成功仍然是一项重大挑战。过去四十年来,包括肿瘤疫苗、TIL疗法和TCR疗法在内的多种免疫治疗策略已在部分实体瘤中展现出临床疗效,提示其在特定情境下可能优于CAR-T和CAR-NK细胞疗法。癌症-免疫循环的动态特性,即肿瘤特异性新抗原的持续演变,使肿瘤能够逃避免疫监视。这凸显了快速、准确识别功能性肿瘤新抗原以指导个性化肿瘤疫苗设计的迫切需求。这些疫苗可以基于mRNA、DC或合成肽。在本研究中,我们建立了一个新型平台,整合IP-MS以高效、直接地识别肿瘤特异性新抗原肽。通过将该方法与我们的专有AI预测算法及高通量体外功能验证相结合,我们能够在六周内生成患者特异性新抗原候选物,从而加速个性化肿瘤疫苗的开发。

展开英文摘要原文

While immune cell therapies have transformed cancer treatment, achieving comparable success in solid tumors remains a significant challenge compared to hematologic malignancies like non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). Over the past four decades, various immunotherapeutic strategies, including tumor vaccines, tumor-infiltrating lymphocyte (TIL) therapies, and T cell receptor (TCR) therapies, have demonstrated clinical efficacy in select solid tumors, suggesting potential advantages over CAR-T and CAR-NK cell therapies in specific contexts. The dynamic nature of the cancer-immunity cycle, characterized by the continuous evolution of tumor-specific neoantigens, enables tumors to evade immune surveillance. This highlights the urgent need for rapid and accurate identification of functional tumor neoantigens to inform the design of personalized tumor vaccines. These vaccines can be based on mRNA, dendritic cells (DCs), or synthetic peptides. In this study, we established a novel platform integrating immunoprecipitation-mass spectrometry (IP-MS) for efficient and direct identification of tumor-specific neoantigen peptides. By combining this approach with our proprietary AI-based prediction algorithm and high-throughput in vitro functional validation, we can generate patient-specific neoantigen candidates within six weeks, accelerating personalized tumor vaccine development.

论文信息

作者
Tian H、Li G、Chiu CKC、Li E、Chen Y、Zhu T、Hu M、Wang Y
单位
Translation Innovation center, Shenzhen Bay Laboratory, Shenzhen 518132, Guangdong, China.China
期刊
Cell insight2025 Jun
原文标识
PubMed 40547114 · DOI 10.1016/j.cellin.2025.100251