PO.BCS02.01 · 生物信息与计算

ImmunoVerse-Chat:用于新一代免疫治疗靶点发现的对话式智能体 AI 引擎

ImmunoVerse-Chat: A conversational agentic-AI engine for next-generation immunotherapeutic target discovery

海报缩略图:ImmunoVerse-Chat:用于新一代免疫治疗靶点发现的对话式智能体 AI 引擎
编号 23 展板 8 时间 4/19 02:00–05:00 区域 Section 2 主讲 Aman Sharma, B Eng;M Eng
分会场 Agentic AI in Cancer
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作者与单位 Authors & Affiliations

Aman Sharma1, Guangyuan (Frank) Li2, Xinya Liu2, Mark Yarmarkovich2

1Perlmutter Cancer Center, Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY,2Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY

摘要 Abstract

中文摘要
基于 T 细胞的免疫疗法,如 CAR-T 细胞、BiTEs 以及不断扩展的一类新一代 T 细胞衔接模态,已经彻底革新了癌症治疗,并显著改善了许多患者的疗效。然而,这些疗法的成功从根本上依赖于识别安全的、肿瘤特异性的靶点。但是,目前的实践依赖于劳动密集、繁琐复杂的生物信息学工作,需要深厚的领域专长以及计算科学家与临床医生之间的广泛协调。这些碎片化的工作流程减缓了发现的步伐,并显著延迟了新兴靶点向治疗开发的转化。为克服这些挑战,并受近期大语言模型和智能体 AI 进展的启发,我们开发了 ImmunoVerse-Chat,这是一个交互式智能体框架,将 LLM 驱动的推理与高性能免疫基因组学流程相结合,以简化并加速肿瘤特异性抗原的发现。该框架建立在我们此前构建的 ImmunoVerse 之上——迄今为止最全面的泛癌治疗性 T 细胞靶点资源,涵盖超过 21 种肿瘤、11 类分子事件。这些系统级创新共同使 ImmunoVerse-Chat 能够发现具有临床意义的抗原模式,而这些模式在传统流程中往往被忽视或无法获取。ImmunoVerse-Chat 简化了从原始多组学数据到 pHLA 识别的整个免疫肽组学工作流程,并提供一个交互式的、以推理为驱动的界面,能够快速比较抗原图谱、实时对靶点进行优先级排序,以及评估 T 细胞治疗潜力。通过利用底层的泛癌抗原图谱,该系统借助自动化可视化模块,进一步将这些发现置于组织类型和分子畸变的背景下,以区分共享的和肿瘤限制性的 pMHC 候选物,并发现反复出现的、具有人群相关性的抗原、肿瘤驻留的微生物表位,以及与剪接、免疫调控和内源性逆转录病毒表达相关的分子特征,包括 ERV 衍生的肽段。这些整合的、多层次的洞见直接指导安全、免疫原性强且具有临床意义的 T 细胞靶点的选择。总体而言,ImmunoVerse-Chat 将 AI 推理与多组学深度相结合,构成一个统一、交互式、具有人群感知能力的 T 细胞靶点发现引擎,我们预期该平台的广泛采用将使抗原发现在肿瘤学研究中普及化,并加速新一代免疫疗法的开发。
查看英文原文 English abstract
T-cell based immunotherapies such as CAR-T Cells, BiTEs and an expanding class of next-generation T-cell-engaging modalities, have revolutionized cancer treatment and dramatically improved outcomes for many patients. Yet, the success of these therapies fundamentally relies on identifying safe, tumor-specific targets. However, current practice relies on labor-intensive convoluted bioinformatics efforts that require deep domain expertise and extensive coordination between computational scientists and clinicians. These fragmented workflows slow the pace of discovery and significantly delay the transition of emerging targets into therapeutic development. To overcome these challenges and motivated by recent advances in large language models and agentic AI, we developed ImmunoVerse-Chat, an interactive agentic framework that integrates LLM-driven reasoning with high-performance immunogenomic pipelines to streamline and accelerate tumor-specific antigen discovery. Built upon our previously established ImmunoVerse, the most comprehensive pan-cancer therapeutic T cell targets to date, spanning over 21 tumors, 11 classes of molecular events. Together, these system-level innovations allow ImmunoVerse-Chat to uncover clinically meaningful antigen patterns that are often overlooked or inaccessible to conventional pipelines. ImmunoVerse-Chat streamlines the entire immunopeptidomic workflow from raw multi-omic data to pHLA identification and provides an interactive, reasoning-driven interface that enables rapid comparison of antigen landscapes, real-time target prioritization, and assessment of T-cell therapeutic potential. By leveraging the underlying pan-cancer antigen atlas, the system, through automated visualization modules, further contextualizes these findings across tissue types and molecular aberrations to distinguish shared and tumor-restricted pMHC candidates and uncover recurrent, population-relevant antigens, tumor-resident microbial epitopes, and molecular signatures linked to splicing, immune regulation, and endogenous retrovirus expression, including ERV-derived peptides. These integrated, multi-layered insights directly guide the selection of safe, immunogenic, and clinically meaningful T-cell targets. Overall, ImmunoVerse-Chat combines AI reasoning with multi-omic depth into a unified, interactive, and population-aware engine for T-cell target discovery, and we envision the broad adoption of this platform will democratize antigen discovery across oncology research and accelerate the development of next-generation immunotherapies.
利益披露 Disclosure
A. Sharma, NYU Langone Health Employment, ).

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