Characterization of the Potential Cytotoxicity of Klebsiella pneumoniae Isolated from Colorectal Cancer Patients against a Normal Human Fibroblast Model

Article

作者: Daglioglu, Cenk ; Gormez, Arzu ; Kaci, Fatma Necmiye

Colorectal cancer is one of the most common types of cancer worldwide, with a multifactorial digestive pathology. Evidence has suggested that gut microbial dysbiosis is connected to the development of colorectal cancer by generating cancer cell-conducive microenvironments. Nevertheless, the relationship between colorectal cancer pathogenesis and microorganisms has not been fully clarified to date. Here, we addressed this issue and determined the cancer-causing potential of the culture filtrate and proteins of Klebsiella pneumoniae on healthy cells. In this study, the culture filtrate and total proteins of K. pneumoniae isolated from patients with colorectal cancer were investigated to determine their cytotoxic effects against the normal human fibroblast PCS-201-012 cell model. As a result of the isolation procedure, three different K. pneumoniae strains (named Kp1, Kp2, and Kp3) were obtained from biopsy samples. Their 16S rRNA gene sequences were submitted to the GenBank database under the accession numbers MK156319, MK156320, and MK156321, respectively. The WST-8 and hemolysis tests were performed to examine the exacerbating effect of these strains on normal cells. The apoptosis-inducing ability of the isolated strains was characterized based on a combination of several techniques: determination of caspase-3 activity, JC-1 mitochondrial assay, and flow cytometry-based FITC-Annexin-V/PI double staining. Moreover, the expression profiles of four candidate genes (APC, SMAD, KRAS, TP53), which play important roles in the development of colorectal cancer, were analyzed by the qRT-PCR method. Cell biology experiments demonstrated that the culture filtrate and proteins of the related strains clearly cause cell death in normal human fibroblasts due to increased inflammatory response and necrosis. Furthermore, the culture filtrates and proteins led to a decrease in the expression of tumor suppressor genes TP53, SMAD, and APC and an increase in the expression of the KRAS oncogene, emphasizing the tumorigenicity of the strains in colorectal cancer. These results revealed that K. pneumoniae strains are capable of triggering cytotoxicity in normal human fibroblast cells.

2025-01-01·NATURE BIOTECHNOLOGY

Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy

Article

作者: Lindner, K ; Haltenhof, G ; Harbottle, R P ; Poschke, I ; Green, E W ; Ratliff, M ; De Roia, A ; Rodriguez Ehrenfried, A ; Bunse, L ; Platten, M ; Boschert, T ; Faenza, A ; Imperatore, F ; Meng, Z ; Tan, C L ; Offringa, R ; Lindner, J M

Abstract:

The identification of patient-derived, tumor-reactive T cell receptors (TCRs) as a basis for personalized transgenic T cell therapies remains a time- and cost-intensive endeavor. Current approaches to identify tumor-reactive TCRs analyze tumor mutations to predict T cell activating (neo)antigens and use these to either enrich tumor infiltrating lymphocyte (TIL) cultures or validate individual TCRs for transgenic autologous therapies. Here we combined high-throughput TCR cloning and reactivity validation to train predicTCR, a machine learning classifier that identifies individual tumor-reactive TILs in an antigen-agnostic manner based on single-TIL RNA sequencing. PredicTCR identifies tumor-reactive TCRs in TILs from diverse cancers better than previous gene set enrichment-based approaches, increasing specificity and sensitivity (geometric mean) from 0.38 to 0.74. By predicting tumor-reactive TCRs in a matter of days, TCR clonotypes can be prioritized to accelerate the manufacture of personalized T cell therapies.

2024-02-02·Science advances

H3K27M neoepitope vaccination in diffuse midline glioma induces B and T cell responses across diverse HLA loci of a recovered patient

Article

作者: Green, Edward W. ; Jähne, Kristine ; Platten, Michael ; Boschert, Tamara ; Sahm, Katharina ; Lindner, Katharina ; Poschke, Isabel ; Bunse, Lukas ; Mildenberger, Iris ; Eisele, Philipp ; Haltenhof, Gordon ; Lerner, Taga ; Kromer, Kristina ; Grassl, Niklas ; Lindner, John M. ; Tan, Chin Leng

H3K27M, a driver mutation with T and B cell neoepitope characteristics, defines an aggressive subtype of diffuse glioma with poor survival. We functionally dissect the immune response of one patient treated with an H3K27M peptide vaccine who subsequently entered complete remission. The vaccine robustly expanded class II human leukocyte antigen (HLA)–restricted peripheral H3K27M-specific T cells. Using functional assays, we characterized 34 clonally unique H3K27M-reactive T cell receptors and identified critical, conserved motifs in their complementarity-determining region 3 regions. Using detailed HLA mapping, we further demonstrate that diverse HLA-DQ and HLA-DR alleles present immunogenic H3K27M epitopes. Furthermore, we identified and profiled H3K27M-reactive B cell receptors from activated B cells in the cerebrospinal fluid. Our results uncover the breadth of the adaptive immune response against a shared clonal neoantigen across multiple HLA allelotypes and support the use of class II–restricted peptide vaccines to stimulate tumor-specific T and B cells harboring receptors with therapeutic potential.

项与 BioMed X GmbH 相关的新闻（医药）

2026-04-16

·BioSpace

BioMed X and Servier Launch First Research Team in France to Pioneer AI-Driven Antibody Engineering

· New XSeed Labs team at Servier’s Paris-Saclay campus brings together AI and immunology expertise to advance next-generation biologics. Paris-Saclay, France, April 16, 2026 – BioMed X , a leading innovation hub for pharma, has officially launched its first research team at BioMed X France, marking the establishment of its presence in one of Europe’s fastest-growing life science ecosystems. The new team, Team ADB (AI-Empowered Design of Bispecific Antibodies) , is based within the XSeed Labs incubator on the R&D campus of Servier in Paris-Saclay and hosted at the Spartners facility operated by Servier and BioLabs. Bispecific antibodies represent one of the most promising classes of biologic therapeutics, capable of engaging two molecular targets simultaneously and enabling new treatment strategies across oncology, immunology, and other complex disease areas. However, their engineering remains challenging due to structural constraints, limited predictability of dual-target interactions, and the need to optimize stability, specificity, and manufacturability. The research team is led by Dr. Tomabu Adjobimey , an immunologist with a strong record in host-pathogen interactions and immune system modulation. Dr. Adjobimey holds the academic rank of Associate Professor in Immunology and Microbiology at the University of Abomey-Calavi, Benin, and previously led the Human Immunology Group at the Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Germany. Dr. Tomabu Adjobimey , Group Leader of Team ADB , said: “Our goal is to develop an AI-driven platform that integrates structural modeling, machine learning, and experimental validation to guide the rational design of bispecific antibodies. By enabling more predictive and structure-aware antibody engineering, this approach could significantly accelerate the discovery of innovative biologic therapeutics addressing major unmet medical needs.” BioMed X France is led by Dr. Paula Wagner Egea , Managing Director and Site Head, a protein engineer and biotech entrepreneur with a background in de novo protein design and artificial metalloenzyme engineering. She earned her Ph.D. in Biochemistry from the Technical University of Munich (TUM) and brings more than seven years of international R&D experience across Europe and the United States. Dr. Paula Wagner Egea, Managing Director and Site Head of BioMed X France , said: “The launch of this XSeed Labs team represents an important milestone for BioMed X as we establish our presence in France. We are creating a unique environment for interdisciplinary innovation at the intersection of artificial intelligence and biomedical research. With Team ADB and our partners at Servier, we are bringing fresh thinking to one of the most exciting frontiers in immuno-oncology.” Dr. Clément Barjon, Research Project Leader, Immuno-Oncology , Institut de R&D Servier Paris-Saclay , also commented: “Bispecific antibodies have become a defining modality in modern oncology, enabling precise immune redirection and multi‑pathway targeting that can deliver deep clinical responses. However, they require sophisticated engineering, where selecting and optimally pairing binding domains remains largely empirical and difficult to predict. By partnering with BioMed X, we aim to systematically tackle this challenge.” About BioMed X BioMed X is a leading innovation hub for pharma. With our global network of research institutes at top universities and incubators within pharmaceutical companies, we bridge the gap between academia and industry. We are pioneers in applying the principles of design thinking and crowdsourcing to drug discovery and development. With our unique model, we identify key challenges across all therapeutic areas, recruit top academic talent, and co-create tailored solutions with our pharma partners. In our stimulating ecosystem, early-career researchers grow into future scientific leaders. They perform exploratory research, deliver industry-grade results, and pave the way to next-generation therapies. At BioMed X, we value curiosity, diversity, and purpose. Our goal is to serve as a vital catalyst for innovation in global health for the benefit of all patients. PRESS CONTACT Maria Morganti BioMed X VP, Head of Marketing & Communications +49 6221 42611 30 mm@bmedx.com

2026-01-27

·bmedx.com

BioMed X Launches First Research Project in Partnership with the Government of Barbados to Advance Therapy of Early Diabetic Kidney Disease

The new project, supported by the European Union’s PharmaNext Programme, focuses on population-specific molecular profiling and AI-driven precision medicine for patients of African descent Bridgetown, Barbados, January 27, 2026 – BioMed X, a leading innovation hub for pharma, today announced the launch of its first research project in partnership with the Government of Barbados and with support from the European Union’s PharmaNext Programme. The new global call for research proposals, entitled “AI-Enabled Therapy of Early Diabetic Kidney Disease in Barbados,” addresses one of the most pressing and underexplored challenges in cardiometabolic disease: the biological heterogeneity of early diabetic kidney disease in the Barbadian population. The objective of this project is to understand the molecular mechanisms driving early diabetic kidney disease in individuals with Type 2 Diabetes in Barbados through deep molecular profiling and advanced AI-based modeling. By combining multi-layer molecular characterization of Barbadian patients and healthy controls with AI-driven modeling, the project aims to construct a population-specific digital African twin. This model is intended to enable refined patient stratification, improved biomarker discovery, and adaptive, data-driven therapeutic strategies. Call for Application BioMed X, together with its public-sector and European partners, invites bold and interdisciplinary research proposals that focus on the following key deliverables: Focused molecular profiling of Barbadian Type 2 Diabetes patients with early diabetic kidney disease and matched healthy controls. Development of an AI-driven digital African twin model capturing population-specific molecular heterogeneity, disease trajectories, and predictive stratification features. Identification and validation of novel molecular biomarkers to inform personalized diabetic kidney disease risk assessment and treatment adaptation in Barbados. Original ideas reaching far beyond the current state of the art are particularly encouraged. A New Model for Public-Private Collaboration This initiative marks an important milestone for BioMed X, extending its established collaboration model into a direct partnership with a national government to address population-specific health challenges. Leisel Juman, CEO of BioMed X Barbados, commented: “By partnering directly with the Government of Barbados and with support from the European Union, we are applying our global talent-sourcing and incubation model to a real-world public health challenge in an underrepresented population. This initiative creates a structured pathway from fundamental discovery to real-world impact – while equipping Barbados with the capabilities to contribute meaningfully to the global innovation landscape.” Jonathan Reid, Minister of Innovation, Industry, Science and Technology, added: “This launch reflects our commitment to positioning science and technology at the heart of Barbados’ future. Through collaboration, talent development, and early engagement of our young people, we are laying the groundwork for an innovation ecosystem that is globally connected and capable of driving sustainable national growth.” H.E. Fiona Ramsey, EU Ambassador to Barbados, said: “Through the PharmaNext Programme, the European Union is committed to supporting innovative research partnerships that address global health challenges while strengthening scientific capacity. This project exemplifies how European support, local leadership, and international scientific excellence can come together to deliver impactful, inclusive innovation.” Are you interested in applying? Please check our Career Space here. Previous Press Release BioMed X Launches XBridge Pilot to Facilitate Industry-Academic Research Collaborations Jan 13, 2026 Next Press Release BioMed X Appoints Former Max Planck Institute Head of Administration Nico Frisch as Vice President, Site Head Heidelberg Feb 4, 2026

2026-01-26

·Bio-centrix

口服环肽/多肽药物的多份研报解读

口服环肽药物正颠覆百年制药规则——分子量突破传统限制，甚至疗效媲美注射剂，患者依从性将迎来质的飞跃。默沙东口服PCSK9环肽抑制剂Ⅲ期临床降低血脂超60%，强生口服IL-23小肽拮抗剂冲击50亿美元市场，而博瑞医药的双靶点GLP-1/GIP口服药已获批临床，全球竞速开启。研报原文和根据研报整理的音频播客，放在文末。下面是针对口服环肽/多肽药物的多份研报解读：【研发人员重点关注】 • 从“序列发现”向“架构工程”跨越：2026年被定义为“改性多肽”之年，研发重点已从寻找新序列转向通过分子工程提升药物稳定性。例如，MBX Biosciences的PEP™平台利用糖基共轭技术，能将多肽半衰期从几分钟延长至数周，使天然序列在长期控制研究中趋于过时。 • 口服递送技术的路径分化：目前存在两种主流竞争方案：一是如诺和诺德Rybelus使用的渗透促进剂（SNAC）；二是Protagonist Therapeutics开发的富含二硫键多肽（DRPs），这种“笼状”结构通过分子本身的刚性抵御胃酶降解，无需额外添加促进剂。 • 小分子模拟肽的替代趋势：Crinetics Pharmaceuticals等公司正开发能模拟多肽结合位点的非肽类小分子药物（如口服SSRA药Paltusotine），这为研发人员提供了新的思路：通过彻底改变分子的化学性质来规避多肽的降解问题。 • 单克隆抗体（mAb）的口服突破：由于抗体分子量巨大（约150 kDa），传统吸收极难（生物利用度仅约0.02%）。Biora Therapeutics的BioJet™智能胶囊通过“液体喷射”技术将药物直接注入小肠壁，在猪模型中实现了高达80%的系统生物利用度，且无需重新进行药物剂型改造。 • 靶向α疗法（TAT）的载体选择：在放射性药物研发中，双环肽（Bicyclic Peptides）因渗透快、肾脏清除快，正取代循环时间过长的抗体，成为承载Lead-212等同位素精准打击肿瘤的理想载体。 • 儿童用药制剂的特殊要求：针对无法吞咽大型胶囊的儿童群体，研发方向正转向口服崩解片（ODTs）、多颗粒撒剂或咀嚼片，且优先使用**食品级蛋白质（如酪蛋白）**作为纳米载体，因其具有天然的生物相容性和安全性。 • 临床试验设计新指标：以Icotrokinra（JNJ-2113）为例，其Phase 3 ICONIC-TOTAL研究通过使用部位特异性评分（如ss-IGA针对头皮、sPGA-G针对生殖器），证明了口服多肽在治疗难治区域银屑病方面的独特优势【投资者决策参考】 • 口服生物药的“营收超级周期”：全球口服蛋白质与多肽市场预计将从2024年的80.5亿美元增长至2034年的363.5亿美元，年复合增长率（CAGR）高达16.34%。这一趋势标志着此类药物正从昂贵的“特种药”向“大众市场”模式转型。 • 代谢与肥胖赛道的统治力：代谢性疾病细分市场在2024年占据了46%的市场份额。随着GLP-1药物适应症扩展至睡眠呼吸暂停、心衰和肾脏疾病，其总潜在市场（TAM）大幅扩张，预计到本十年末销售额将接近2000亿美元。 • 并购（M&A）的主要驱动力：大型药企面对2028-2029年的“专利悬崖”，正利用充沛现金流收购口服递送平台。2025年已出现多起重磅交易，如默克（Merck）以4.93亿美元签署口服技术授权协议，阿斯利康投资500亿美元用于包括多肽在内的研发生产。 • 竞争格局的“二元化”：诺和诺德与礼来通过供应链扩张和口服专利建立了强大的“护城河”。投资者应警惕由于美国FDA宣布Semaglutide短缺解决而对“影子市场”（如仿制配方药房）造成的致命打击，建议转向投资拥有专利技术的龙头企业。 • 产业链底层的“卖水人”：由于口服药物所需的原料药（API）体积远超注射剂，产能成为核心瓶颈。CDMO巨头如Bachem和CordenPharma通过锁定长期生产合同，正从这场多肽战争中稳健获利，不受具体哪款药物胜出的影响。 • 政策与定价风险：随着Medicare对减肥药支出飙升，*价格谈判（IRA）*和政治压力是2025年后影响行业利润率的最大单一风险。【高校科研方向参考】 • 基础研究突破：FcRn介导的转运机制：高校研究者正探索如何通过重组技术重新设计抗体，使其在更宽的pH范围内与**新生儿Fc受体（FcRn）**结合，利用人体肠道天然存在的跨细胞转运途径实现单抗的全身吸收。 • 新靶点发现与结构生物学：针对“难成药”靶点（如细胞因子、GPCRs、离子通道），利用mRNA展示、DNA编码库（DEL）以及计算匹配技术（如Vectrix™）从头筛选构象受限的多肽支架，是当前学术界转化的热点。 • 多学科交叉：智能机器人胶囊：结合机械工程、生物传感器与材料科学，研发具有自动定位功能（仿生豹纹陆龟形状实现自动翻正）和由pH触发的机械式微注射器，这是解决生物大分子吸收障碍的跨界方案。 • 肠道滞留技术的合作机遇：诺和诺德与BioMed X的合作项目专注于“延长多肽在下小肠的部位特异性滞留”，旨在通过新型配方延长吸收窗口，这为高分子材料和消化系统生理学研究者提供了产学研合作空间。 • 生物标记物的临床意义转化：研究显示hsCRP（超敏C反应蛋白）作为炎症和心血管风险的核心指标，在新型NLRP3抑制剂（如BGE-102）的 Phase 1 试验中降幅达86%，这证明了针对特定生物标记物的转化研究具有高度的商业前景。 • 药动学建模的需求：目前学术界迫切需要建立可靠的体外-体内相关性（IVIVC）模型，以准确预测不同饮食状态（进食与空腹）对口服蛋白质吸收的影响，这是从实验室原型走向商业规模生产的关键缺失环节。 • 放射性核素的精准递送：在肿瘤学研究中，研究重点正转向“螯合剂就绪肽”（Chelator-Ready Peptides），即预先结合了DOTA或NOTA等“金属笼”的多肽，以便快速装载放射性同位素进行分子影像或治疗研究。根据研报整理的音频播客：部分参考资料： 2025-11-22-华创证券-华创医药投资观点_研究专题周周谈第151期_多款口服环肽药物具重磅潜力_产业链有望充分受益 20240318-华创证券-创新药周报_强生口服IL-23R多肽拮抗剂治疗银屑病长期疗效积极 20250716-东吴证券-博瑞医药-688166.SH-在研管线进展点评_BGM0504片IND申请获受理_稀缺双靶点口服多肽即将进入临床

放射疗法临床3期

100 项与 BioMed X GmbH 相关的药物交易

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100 项与 BioMed X GmbH 相关的转化医学

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