撰文丨王聪 编辑丨王多鱼 排版丨水成文 Notch 信号通路 是一种进化上最保守的信号通路之一，在免疫细胞、神经元、血管内皮细胞、心肌细胞以及其他细胞谱系中是关键的发育命运决定因子，尤其是 T 细胞 的 发育和功能。 在体外从祖细胞/干细胞分化生成许多细胞类型都需要激活 Notch 信号通路。然而，在实验室中模拟这种高度机械性、依赖接触的信号通路，一直是个巨大的挑 战。 2025 年 8 月 1 日，哈佛大学医学院/波士顿儿童医院 George Daley 团队联合诺奖得主、蛋白质设计先驱 David Baker 教授，在国际顶尖学术期刊 Cell 上发表 了题为 ： Design of soluble Notch agonists that drive T cell development and boost immunity 的研究论文。 该研究利用 David Baker 教授团队开发的 AI 蛋白 设计工具 Rosetta ，成功设计生成了全球首个 可溶性 Notch 激动剂 ，这种可溶性蛋白能够在悬浮培养中模拟 Notch 信号通路的激活，实现了 T 细胞高效分化，并显著增强了 T 细胞功能及其抗肿 ...

Summary of Marker Therapeutics Conference Call Company Overview - **Company**: Marker Therapeutics - **Industry**: Biotechnology, specifically focused on T cell therapies for cancer treatment Key Points and Arguments Clinical Trial Updates - **Phase II AML Trial**: Marker Therapeutics is advancing its Phase II trial for acute myeloid leukemia (AML) with its lead product candidate, MT-401, which is a multi TAA specific T cell therapy [4][5] - **Initial Results**: The safety lead-in portion of the trial showed a strong safety profile with no serious adverse events (SAEs) or neurotoxicity observed. One patient with measurable residual disease (MRD) converted to MRD negative status after treatment [5][6][25] - **Patient Demographics**: The trial plans to enroll approximately 180 patients, with a median age of 52, heavily pretreated with prior therapies [10][13] Manufacturing Process Improvements - **New Manufacturing Process**: A new T cell manufacturing process has been developed that reduces the manufacturing time to nine days, significantly improving potency and tumor-killing capabilities [7][28][33] - **Potency Increase**: The new process yields a product that is four times more potent based on antigen specificity compared to previous methods [30][33] - **Scalability**: The new process allows for pre-manufacturing of cell bank inventory, enabling faster delivery to patients within approximately 72 hours [39][40] Pipeline Expansion - **New Trials**: Marker plans to initiate three additional clinical trials over the next twelve months, including studies in pancreatic cancer and lymphoma, utilizing the new MT-601 product [43][44] - **Off-the-Shelf Products**: The company is expanding its pipeline to include off-the-shelf therapies, which will allow for broader patient access and treatment options [8][41] Safety and Efficacy - **Safety Profile**: No dose-limiting toxicities or cytokine release syndrome were noted in the safety lead-in results, consistent with previous studies [25][26] - **Efficacy in MRD Positive Patients**: The results support further investigation of MT-401 in AML patients, particularly in the MRD positive population, which currently lacks effective treatment options [25][84] Future Plans - **Clinical Goals**: The company aims to fully implement the new manufacturing process into the current AML study and complete dose escalation cohorts by Q3 2022 [45] - **IND Filings**: Plans to file Investigational New Drug (IND) applications for new studies are projected for the fourth quarter of 2022 [46] Additional Important Information - **Regulatory Considerations**: The company has worked closely with the FDA to ensure that the new manufacturing process meets regulatory standards for clinical studies and future commercialization [90] - **Patient Selection**: The company is cautious about identifying specific patient populations for therapy, emphasizing the need for further data to understand the therapy's effectiveness across different patient groups [80][82] This summary encapsulates the key points discussed during the Marker Therapeutics conference call, highlighting the company's advancements in clinical trials, manufacturing processes, and future plans in the biotechnology sector.