Sanyou Biopharmaceuticals Co., Ltd.

作者：刘亚楠 仲鑫汝 美工：何国红 罗真真 排版：马超 新闻速递 ▼ 2025年7月22日，世界卫生组织（WHO）针对基孔肯雅热（CHIKV）全球传播风险发布警报，全球已有119个国家和地区报告了基孔肯雅热的本地传播，约550万人面临感染风险，WHO呼吁各国强化蚊媒控制与临床监测。广东省疾控局通报，2025年7月27日0时至8月2日24时全省新增本地确诊病例2892例，累计报告病例7000多例。为应对这一公共卫生挑战，三优提供多种针对CHIKV的中和抗体、重组蛋白产品，为疫苗、抗病毒药物、诊断试剂研发提供全面支持。 三优生物CHIKV抗体 ▲ 扫码访问官网浏览产品详情 三优生物CHIKV重组蛋白 ▲ 扫码访问官网浏览产品详情 关于基孔肯雅热病毒 基孔肯雅热（Chikungunya fever）是由基孔肯雅病毒（Chikungunya virus，CHIKV）感染引起，经伊蚊叮咬传播的急性传染病。基孔肯雅病毒（Chikungunya virus, CHIKV）隶属于披膜病毒科甲病毒属，其名称源自非洲坦桑尼亚的马孔德语，意为“弯腰驼背”，生动刻画了感染者因剧烈关节疼痛而难以直立的痛苦状态。该病毒主要借由埃及伊蚊（Aedes aegypti）和白纹伊蚊（Aedes albopictus）的叮咬扩散，临床上以突发高热、斑丘疹及对称性多关节疼痛为典型三联征。尽管基孔肯雅热的病死率相对较低，但患者常遭受剧烈的关节疼痛困扰，更有相当比例的病例会进展为持续数月乃至数年的慢性关节炎，不仅严重降低患者生活质量，还带来沉重的社会经济负担。 CHIKV的病毒结构与基因组 CHIKV是有包膜的球形颗粒，直径约60-70纳米，含有5个结构蛋白（衣壳蛋白C、包膜蛋白E1、E2、E3以及转框蛋白TF）和4个非结构蛋白（nsP1、nsP2、nsP3和nsP4），CHIKV结构蛋白E1和E2在病毒颗粒表面形成三聚体的“病毒刺突”，在病毒附着、入侵及诱导宿主免疫应答中发挥关键作用。其中E2蛋白负责与宿主细胞受体结合，E1蛋白介导病毒包膜与宿主细胞膜的融合，而病毒颗粒中含有的E3和6K小分子蛋白，则辅助结构蛋白的折叠、运输及病毒颗粒的组装出芽。 CHIKV的基因组是一条长度约11.8 kb的单股正链RNA，可直接作为信使RNA翻译蛋白质，其两端分别带有与真核生物mRNA相似的5'端帽子结构（m7GpppN）和3'端poly(A)尾，便于在宿主细胞内被核糖体识别翻译；基因组包含两个大的开放阅读框（ORF），5'端约三分之二的ORF编码非结构多聚蛋白P1234，经病毒自身蛋白酶切割为nsP1、nsP2、nsP3、nsP4四个非结构蛋白，共同组成RNA复制酶复合体，3'端约三分之一的ORF编码结构多聚蛋白，经宿主蛋白酶切割产生衣壳蛋白C及E3、E2、6K、E1等结构蛋白，这种基因组结构与表达策略是甲病毒属的典型特征。 ▲ CHIKV病毒结构以及入侵机制 CHIKV临床进展 全球已有两款基孔肯雅病毒疫苗获批上市，分别为Ixchiq和Vimkunya。Ixchiq是一种减毒活疫苗在nsP3蛋白的超变区缺失了60个氨基酸，在复制效率上显著低于野生型CHIKV，2023年起先后在美国、欧盟及加拿大获批，单剂接种安全性与免疫原性良好，中和抗体可维持至少12个月，主要不良反应为头痛、疲劳等，适用于18岁及以上人群。Vimkunya为病毒样颗粒重组疫苗，2025年2月获得美国FDA批准上市，含基孔肯雅病毒样颗粒，由衣壳蛋白、E1和E2蛋白组成，单剂接种可诱导持续2年的抗体应答，适用于12岁及以上人群，不良反应轻至中度。 其他候选疫苗涵盖载体疫苗、mRNA疫苗、灭活疫苗等，部分进入临床阶段，灭活疫苗因安全性较高更适用于特殊人群，但免疫原性较低。治疗方面，目前尚无获批特效药，以对症缓解为主，部分化合物及单克隆抗体在实验中显示抗病毒活性，单克隆抗体可通过中和病毒或抑制受体结合发挥作用，但其成本与储存要求可能限制在中低收入地区的应用，且疫苗及候选疗法是否引发抗体依赖增强效应仍需研究。 ▲ 临床在研药物 关于三优 三优生物作为专注创新抗体药物研发与服务的先锋企业，在新冠、猴痘、基孔肯雅热等疫情来袭时，始终以全球疫情防控需求为导向，凭借专业研发实力快速响应，高效研发推出针对相关病毒的抗原与抗体，为疫苗研发、抗病毒药物开发及诊断试剂研制提供了全方位支持。 参考文献 1. de Souza, William M et al. “Chikungunya virus and other emerging arthritogenic alphaviruses.” Nature reviews. Microbiology, 10.1038/s41579-025-01177-8. 7 May. 2025, doi:10.1038/s41579-025-01177-8 2. Hakim MS, Aman AT. Understanding the Biology and Immune Pathogenesis of Chikungunya Virus Infection for Diagnostic and Vaccine Development. Viruses. 2022 Dec 23;15(1):48. 3. Huerta Albarran R, Weber A, Aviles Robles M, et al. Chikungunya virus infection: A scoping review highlighting pediatric systemic and neurologic complications[J]. Semin Pediatr Neurol, 2025, 54: 101213. Cut off the CHIKV infection chain with Sanyou neutralizing antibodies NEWS ▼ On July 22, 2025, the World Health Organization (WHO) issued an alert regarding the global spread risk of chikungunya (CHIKV). To date, 119 countries and regions worldwide have reported local transmission of chikungunya, with approximately 5.5 million people at risk of infection. The WHO urged all countries to strengthen mosquito vector control and clinical surveillance.The Guangdong Provincial Center for Disease Control and Prevention announced that from 00:00 on July 27 to 24:00 on August 2, 2025, the province recorded 2,892 new local confirmed cases, bringing the cumulative number of reported cases to over 7000. To address this public health challenge,  Sanyou offers a range of CHIKV-targeting neutralizing antibodies and recombinant protein products, providing comprehensive support for the research and development of vaccines, antiviral drugs, and diagnostic reagents. CHIKV Antibodies ▲ Scan the QR code to visit the official website and view product details CHIKV Recombinant Protein ▲ Scan the QR code to visit the official website and view product details About Chikungunya Virus Chikungunya fever is an acute infectious disease caused by Chikungunya virus (CHIKV) and transmitted via the bite of Aedes mosquitoes. Chikungunya virus (CHIKV) belongs to the genus Alphavirus within the family Togaviridae. Its name is derived from the Makonde language of Tanzania, Africa, meaning "that which bends up"—a vivid description of the painful state of infected individuals, who struggle to stand upright due to severe joint pain.The virus is primarily transmitted through the bites of Aedes aegypti and Aedes albopictus. Clinically, it is characterized by the classic triad of sudden high fever, maculopapular rash, and symmetric polyarthralgia. Although the fatality rate of chikungunya is relatively low, patients often suffer from severe joint pain. Moreover, a significant proportion of cases progress to chronic arthritis lasting for months or even years, which not only severely impairs patients' quality of life but also imposes a heavy socioeconomic burden. Structure and Genome of CHIKV CHIKV is an enveloped spherical particle with a diameter of approximately 60-70 nanometers. It contains 5 structural proteins (capsid protein C, envelope proteins E1, E2, E3, and transframe protein TF) and 4 non-structural proteins (nsP1, nsP2, nsP3, and nsP4). The structural proteins E1 and E2 of CHIKV form trimeric "viral spikes" on the surface of the viral particle, playing a key role in viral attachment, entry, and induction of host immune responses. Specifically, the E2 protein is responsible for binding to host cell receptors, while the E1 protein mediates the fusion of the viral envelope with the host cell membrane. Additionally, the small-molecule proteins E3 and 6K contained in the viral particle assist in the folding and transport of structural proteins, as well as the assembly and budding of viral particles. The genome of CHIKV is a single-stranded positive-sense RNA molecule approximately 11.8kb in length, which can directly serve as messenger RNA for protein translation. Its two ends feature a 5' cap structure (m7GpppN) and a 3' poly(A) tail, similar to those of eukaryotic mRNA, facilitating recognition and translation by ribosomes in host cells. The genome contains two large open reading frames (ORFs): the ORF occupying approximately two-thirds of the 5' end encodes the non-structural polyprotein P1234, which is cleaved by viral proteases into four non-structural proteins (nsP1, nsP2, nsP3, and nsP4) that together form the RNA replicase complex. The ORF accounting for approximately one-third of the 3' end encodes the structural polyprotein, which is cleaved by host proteases to generate the capsid protein C and structural proteins such as E3, E2, 6K, and E1. This genomic structure and expression strategy are typical characteristics of the genus Alphavirus. ▲ CHIKV Viral Structure and Entry Mechanism Clinical Progress on CHIKV Two chikungunya virus vaccines have been approved for marketing globally, namely Ixchiq and Vimkunya.Ixchiq is a live-attenuated vaccine with a 60-amino-acid deletion in the hypervariable region of the nsP3 protein, exhibiting significantly lower replication efficiency than wild-type CHIKV. Since 2023, it has been successively approved in the United States, the European Union, and Canada. Single-dose administration demonstrates good safety and immunogenicity, with neutralizing antibodies persisting for at least 12 months. Major adverse reactions include headache and fatigue, and it is indicated for individuals aged 18 years and older.Vimkunya is a recombinant virus-like particle (VLP) vaccine. Approved for marketing by the US FDA in February 2025, it contains chikungunya virus-like particles composed of capsid protein, E1, and E2 proteins. Single-dose administration induces antibody responses lasting for 2 years, is indicated for individuals aged 12 years and older, and is associated with mild to moderate adverse reactions. Other candidate vaccines include vector vaccines, mRNA vaccines, and inactivated vaccines, with some entering clinical stages. Inactivated vaccines, due to their higher safety profile, are more suitable for special populations but have lower immunogenicity.In terms of treatment, there are currently no approved specific drugs, and management primarily focuses on symptomatic relief. Some compounds and monoclonal antibodies have shown antiviral activity in experiments. Monoclonal antibodies exert their effects by neutralizing the virus or inhibiting receptor binding; however, their costs and storage requirements may limit their application in low- and middle-income regions. Additionally, whether vaccines and candidate therapies induce antibody-dependent enhancement (ADE) remains to be investigated. ▲ Drugs in Clinical Development About Sanyou As a pioneering enterprise specializing in the R&D and services of innovative antibody drugs, Sanyou has always been guided by the needs of global epidemic prevention and control when facing epidemics such as COVID-19, monkeypox, and chikungunya. Leveraging its professional R&D capabilities, it responds swiftly and efficiently develops and launches antigens and antibodies targeting these viruses, providing comprehensive support for vaccine R&D, antiviral drug development, and diagnostic reagent development. References 1. de Souza, William M et al. “Chikungunya virus and other emerging arthritogenic alphaviruses.” Nature reviews. Microbiology, 10.1038/s41579-025-01177-8. 7 May. 2025, doi:10.1038/s41579-025-01177-8 2. Hakim MS, Aman AT. Understanding the Biology and Immune Pathogenesis of Chikungunya Virus Infection for Diagnostic and Vaccine Development. Viruses. 2022 Dec 23;15(1):48. 3. Huerta Albarran R, Weber A, Aviles Robles M, et al. Chikungunya virus infection: A scoping review highlighting pediatric systemic and neurologic complications[J]. Semin Pediatr Neurol, 2025, 54: 101213. 推荐阅读 三优十周年｜服务篇-靶点至PCC药物研发 三优十周年｜靶点篇-六大恶性肿瘤靶点介绍创新前沿｜2025ADC热门靶点与技术创新启示三优十周年｜AI-STAL篇-高等电点单域抗体库 6类分子形式之环状多肽分子产生系统解决方案 轻松玩转三优oneClick+线上9大云程序 6类分子形式之mRNA分子产生系统解决方案 三重好礼相送暨四种抗体制备解决方案全新上线 三优生物单域抗体产生系统解决方案 三优生物双抗参比品网站SY-BsAb正式上线 三优ADC药物研发系统解决方案 三优生物oneClick+平台再次上新 三优磁阵列全人源小鼠抗体发现平台重磅发布 三优超万亿全人单克隆抗体产生平台盘点 三优磁阵列全人源小鼠抗体发现平台隆重上线 关于三优生物 三优生物是一家以“让天下没有难做的创新生物药”为使命，以超万亿分子库和人工智能技术双驱的生物医药智能高新技术企业。 公司以智能超万亿分子库为核心，打造了干湿结合、国际领先的创新生物药临床前智能化及一体化研发平台，通过“新药发现、临床前研究、智能化药物研发及前沿科学研究”等四个维度加速全球新药发现及靶标深度研究。 公司总部位于中国上海，在美国、欧洲等地设有子公司，现有投产及布局的研发及GMP场地20000多平方米。 公司为合作伙伴提供“差异化CRO、整合型CDO、协同型CPO、特色CRS”于一体的“创新生物药4C综合业务”。公司已建立全球营销网络，已与全球1200多家药企、生技公司等建立了良好的合作关系；已完成了1200多个新药发现及开发服务项目；已完成了50多个合作研发项目，其中9个合作项目已完成临床申报。 公司已获得国家高新技术、上海市专精特新、上海市小巨人和上海“张江之星”企业认定。

作者：于琦 薛超然美工：何国红 罗真真排版：马超01 引言抗体药物的传奇历程始于1975年单克隆抗体技术的诞生，这一里程碑彻底改变了疾病治疗的格局。随后的几十年里，嵌合、人源化及全人源抗体技术的不断突破，持续加速了这一领域的飞速发展。全球现已有超过170种抗体药物获批，广泛应用于肿瘤、自身免疫等重大疾病。抗体药物市场正经历爆发式增长，预计未来几年，抗体药物的市场份额将持续扩大，并有望在2030年突破数千亿美元，前景无限光明。在抗体药物蓬勃发展的浪潮中，三优生物致力于为客户提供从靶点发现到临床前候选药物（PCC）的一站式开发服务，仅需一个靶点，即可交付高质量的PCC分子，整个过程涵盖靶点调研、原材料制备、分子发现与优化、体内外药效评价以及成药性分析等环节。无论是传统的单克隆抗体、创新的双特异性抗体，还是前沿的抗体药物偶联物（ADC），三优生物均可提供定制化解决方案，助力加速创新生物药的研发进程。截至目前，三优生物已完成60余个PCC项目开发，其中10余个项目已进入临床阶段，最快推进至III期临床阶段。02 服务流程三优生物专注于抗体药物研发领域，提供涵盖靶点调研、原材料制备、分子产生、体外药效评价、分子优化、体内药效评价及成药性分析等关键环节的一站式服务。在研发过程中，首先会对靶点进行深入调研，明确其与疾病的相关性及研发价值，从而确定研发方向。随后将制备相关原材料，包括抗原蛋白、细胞株等，为后续研究奠定基础。基于超万亿创新分子库获得候选分子后，进行体外药效学评价，筛选出具有靶点活性的分子并进行特性优化，以进一步提高其生物活性和成药性。经优化后的分子将在动物模型中进行体内药效学验证，最终通过全面的成药性分析评估其安全性、药代动力学等关键特性。▲ Fig. 1 Target to PCC drug development flowchart01靶点调研在药物研发全流程中，靶点调研作为连接基础研究与临床转化的关键环节，具有核心战略意义。针对尚未满足的临床需求，开展创新抗体药物研发的首要步骤即是靶点调研。该环节会系统性地梳理目标靶点的生物学特征、在疾病发生发展中的分子机制，以及相关领域的研究进展与空白。唯有明确靶点的生物学特征、人群分布差异及与其他治疗手段的协同潜力，才能构建从机制创新到临床价值转化的完整逻辑链，让药物真正聚焦于“正确的靶点，正确的患者，正确的疗效”。三优生物在肿瘤、自身免疫性疾病、代谢性疾病、神经系统疾病、眼科疾病、心血管疾病、感染性疾病、衰老相关疾病以及宠物治疗等领域，均配备了经验丰富的高级科学家团队。针对各类靶点，公司已完成300余个靶点的系统性调研工作。目前，三优生物已有10余个项目通过授权转让进入临床阶段，这些成果充分体现了靶点调研的重要价值。▼ Table. 1 Reported IND project cases02原材料制备三优生物已构建了涵盖质粒、蛋白、mRNA、VLP及研究用细胞株等原材料的完整解决方案体系。该平台能够高效制备各类复杂蛋白，包括胞内蛋白、膜蛋白、胞外蛋白等不同细胞定位蛋白，以及GPCR靶点、离子通道靶点、细胞因子等特殊类型蛋白，充分满足客户对高难度蛋白制备的技术需求。三优生物的技术平台已达到行业领先水平，具备年产10万个蛋白和1000株研究用细胞株的制备能力。原材料制备效率卓越：mRNA包装仅需18天即可完成；足量且质检合格的蛋白可在2周内交付；高表达量、高稳定性的研究用细胞株仅需1个月即可获得。团队成员拥有丰富的项目经验，已成功完成500余个阶段性或整体性服务项目，为客户的抗体开发及药物筛选工作提供强有力的技术支持。▲ Fig. 2 Raw material preparation solution03分子产生三优生物建立了具有自主知识产权、各项性能指标全球领先的超万亿级创新分子库，可广泛应用于创新药物发现、诊断试剂开发、检测技术及科研用抗体定制等多个领域。分子库包含全人源抗体、单域抗体、动物免疫抗体和新型分子四大类，通过12种技术路径可产生全人源抗体、单域抗体、鼠源单抗、兔源单抗、双特异性抗体、多克隆抗体、靶向多肽及靶向小型蛋白等多种分子形式。结合一站式高通量自动化筛选平台，显著缩短了筛选周期，能够高效获得具有高亲和力、优异特异性和良好可开发性的候选分子，系统解决各类分子开发难题，有力推动药物研发进程。截止2025年3月份累计已完成900+项目的筛选，以合作开发或授权转让的模式协助客户完成10余个项目的IND申报，共递交国内外专利申请115件，获得专利授权28件。▲ Fig. 3 Diversified sources of molecules04体外药效评价体外药效筛选作为抗体功能评价的核心环节，可显著加速抗体药物的发现、筛选和优化进程。三优生物专注于创新抗体药物研发领域，构建了稳定、高效且可靠的体外药效筛选平台。该平台目前涵盖流式细胞分析、体外药效方法开发、体外药效样品检测及非特异性结合检测等模块，能够确保候选抗体以高效率、高通量和高标准完成体外药效筛选工作。平台建立了数十种多维度、立体化的体外药效评价体系，可满足抗原抗体结合、信号通路调控及细胞功能评估等多层次研究需求。平台目前拥有150余种经项目验证的靶点细胞株、20余种经项目验证的原代细胞、8大类51项子类检测方法，并配备92份标准化操作规程（SOP）支持。常规检测方法仅需1周即可完成，高难度检测方法可在4周内完成；常规方法开发周期为2周，高难度方法开发周期为8周。▲ Fig. 4 Solution for in vitropharmacological evaluation05分子优化三优生物凭借其完善的抗体工程改造技术平台，致力于为客户提供高效、专业的抗体优化服务。该平台涵盖了抗体优化的关键环节，包括人源化改造、亲和力成熟、成药性优化及半衰期延长。平台具有抗体各功能区域的精准改造能力，包括框架区（FR）、互补决定区（CDR）和恒定区（Fc）。通过对这些区域的精细操作，三优生物能够满足多样化的项目需求，并显著提升改造后抗体的性能，包括但不限于药效学与成药性显著提升、交叉反应性增强、靶点特异性改善、潜在修饰风险的消除。三优生物在效率方面处于行业领先地位，每轮抗体改造周期仅需6-8周即可高质量完成，显著加速了客户项目进入后续的功能筛选阶段。该平台由经验丰富的团队支撑，已成功完成500余例各类抗体分子的改造项目。其中，40余个设计抗体已进入临床申报阶段，10余个已进入临床试验阶段，充分验证了其技术平台的可靠性和成功率。▲ Fig. 5 Molecular optimization solutions06体内药效评价体内药效评价作为确定临床前候选分子的关键环节，可进一步验证候选分子在动物模型中的有效性和安全性。三优生物已建立高通量、高质量的候选分子体内药效评价平台，该平台涵盖体内药效方法开发系统、动物药效评价系统、药代动力学研究系统以及急性毒性检测系统。平台以国内外大小动物药效评价市场为核心，重点围绕肿瘤和自身免疫性疾病两大适应症，建立了完善的肿瘤CDx模型体系、自身免疫性疾病非肿瘤模型平台、细胞因子及血液标志物检测系统，且提供从小鼠到非人灵长类动物的完整药代动力学评价服务，全面满足临床前非GLP相关研究需求。目前平台已积累150余个经项目验证的CDx模型、数十种非肿瘤疾病模型、40余项标准操作规程（SOP），并成功支持10余个药效相关临床申报项目。▲ Fig. 6 Solution for in vivo drugefficacy evaluation07成药性分析三优生物经过多年的技术沉淀与升级，已建立起涵盖单抗、多抗和融合蛋白的多维表征分析平台。其中，抗体理化分析平台已开发出10种检测项目，具备多维表征、全面合规、高质高效的特点，可支持生物新药研发前期样品的质量控制。生化分析平台则通过优化各类生化检测方法，进一步丰富了检测内容。基于ELISA的生化分析技术具有周期短、重复性好、通量高、成本低等优势，可高效地从大量先导分子中筛选优质候选分子，显著提升“先导分子聚焦”效率。该技术已成功应用于数百个服务项目，覆盖早期药物研发、小试工艺开发等全研发阶段。同时，平台严格参照药典要求建立了完善的标准体系，凭借精准可靠的表征方法，为药物生产提供技术支持和工艺指导。▲ Fig.7 Solution for drug analysis03 服务特性01全流程覆盖三优生物靶点至PCC药物研发系统解决方案覆盖靶点调研、原材料制备、分子产生、体外药效评价、分子优化、体内药效评价及成药性分析等关键环节，实现研发流程的无缝整合。该模式有效规避了因技术标准差异、数据断层或沟通障碍导致的效率损失，确保从靶点发现到PCC研发的每个环节均能基于前期成果精准递进。通过全流程一体化设计，依托统一的质量控制体系和跨学科协作机制，可早期识别潜在风险（如抗体成药性不足或靶点选择性欠佳等），及时调整研发策略，从而显著缩短研发周期、降低重复投入，最终提高候选抗体的成药成功率，为创新药物研发提供高效可靠的技术支持。▲ Fig.8 Full process coverage02定制化适配三优生物靶点至PCC药物研发系统解决方案能够根据项目靶点特性及研发阶段需求，提供定制化的实验方案与技术路线。针对不同研发阶段和客户核心诉求，平台可动态调整实验方案，避免标准化研发模式导致的资源浪费与效率损失。这种高度灵活的模式既保证了研发策略与靶点生物学特性的精准匹配，又能聚焦项目核心目标，在提升候选抗体成药性的同时有效控制后期开发风险，为创新药物研发提供更加精准高效的解决方案。▲ Fig.9 Research and statistics on100+ targets of Sanyou Biotechnology03高效化推进三优靶点至PCC药物研发系统解决方案整合了多个技术平台与资深团队经验，能通过AI辅助设计和高通量实验平台加速先导分子的筛选效率，结合严格的质量控制体系确保数据可靠性，能在早期同步解决活性、选择性、成药性等关键问题，减少后期返工风险；此外，基于历史项目数据库建立的预测模型，可精准指导实验方向，大幅缩短从靶点到PCC的药物研发周期，降低研发风险，为客户提供从早期探索到候选分子确定的无缝衔接支持。▲ Fig.10 Project operation cycle04 案例展示01抗CTLA4单抗的开发基本信息：CTLA4（细胞毒性T淋巴细胞相关抗原4，CD152）属于免疫球蛋白超家族（IgSF），是一种跨膜蛋白，在细胞外区域含有IgV样结构域，与CD28具有高度同源性（约31%的氨基酸序列相似性）。两者都与抗原呈递细胞（APC）表面的B7分子（CD80/CD86）竞争性结合，但CTLA4具有更高的亲和力（约10-20倍），并通过抑制共刺激信号负调控T细胞活化。分布情况：CTLA4主要在活化的CD4+/CD8+T细胞和调节性T细胞（Treg）的表面表达，特别是在肿瘤微环境中，Treg高度表达CTLA4。竞争格局：根据Insight数据库的调查，全球有139种针对CTLA4的抗体药物正在开发中，其中5种已经上市，1种正在申请上市。首个获得美国食品药品监督管理局批准的CTLA4单克隆抗体（2011年），用于治疗黑色素瘤，2020年全球市场规模为17亿美元Tremelimumab：在癌症等适应症中进行III期临床试验。▲ Fig. 11 Mechanism of action of CTLA402抗CTLA4单抗的关键结果▶ 2.1. 细胞水平的结合活性分析通过三优生物分子产生平台获得的单域抗体候选分子大多具有较好的细胞水平结合活性。Fig. 12A展示了采用FACS分析候选抗体与huCTLA-4 CHO细胞的结合活性，候选抗体与对照抗体相比，具有相当的结合活性。Fig. 12B展示了采用FACS分析候选抗体与cynoCTLA-4 CHO细胞的亲和力测定结果，候选抗体的与对照抗体相比，具有相当的结合活性。▲ Fig. 12 Binding affinity of antibody▶ 2.2. 细胞水平的阻断活性分析采用FACS方法检测候选抗体是否阻断配体CD80-ECD、CD86-ECD与huCTLA-4 CHO细胞的结合。Fig. 13A展示了候选抗体阻断CD80-ECD与huCTLA-4 CHO细胞的结合，阻断效果与对照抗体相当或优于对照抗体。Fig. 13B展示了候选抗体阻断CD86-ECD与huCTLA-4 CHO细胞的结合，阻断效果与对照抗体相当或优于对照抗体。▲ Fig. 13 Blocking activity of antibody ▶ 2.3. 人源化抗体细胞水平的结合活性分析针对NB25B-17和NB25gb-1通过三优生物分子优化平台进行人源化改造。对获得的单域抗体在细胞水平进行结合活性检测。Fig. 14A展示了采用FACS分析候选抗体与huCTLA-4 CHO细胞的亲和力测定结果。Fig. 14B展示了采用FACS分析候选抗体与cynoCTLA-4 CHO细胞的亲和力测定结果。结果表明，NB25B-17-9-H1-IgG1和NB25gb-1-11-H1-IgG1显示出比其他候选抗体更好的结合能力和交叉活性。▲ Fig. 14 Binding affinity of antibody▶ 2.4. 人源化抗体细胞水平的阻断活性分析采用FACS方法检测候选抗体是否阻断配体CD80-ECD、CD86-ECD与huCTLA-4 CHO细胞的结合。Fig. 15A展示了候选抗体阻断CD80-ECD与huCTLA-4 CHO细胞的结合。Fig. 15B展示了候选抗体阻断CD86-ECD与huCTLA-4 CHO细胞的结合。结果表明，NB25B-17-9-H1-IgG1、NB25gb-1-11-H1-IgG1和NB25gb-1-11-H2-IgG1对huCTLA-4 CHO的阻断活性优于对照抗体。▲ Fig. 15 Blocking activity of antibody▶ 2.5. 体内药效评价在HuCTLA4小鼠皮下接种MC38肿瘤细胞，当平均肿瘤体积达到约100 mm3时，将小鼠随机分为4个实验组，其中1组为对照组，3组为给药组，分别给3个不同的剂量。通过腹部给药给予抗体（每周2次，给药三周），在第32天结束给药。当肿瘤细胞进行Anti-CTLA4抗体给药时，发现肿瘤体积明显缩小。▲ Fig. 16 In vivo efficacy of antibody05 总结展望在从靶点到PCC的抗体药物研发全流程中，三优生物依托其超万亿级创新分子库和一体化研发平台优势，已成功完成60余个靶点的项目开发（其中10余个已推进至III期临床阶段）。经过十年深耕，三优生物构建了涵盖靶点调研至PCC交付的一站式、全流程服务体系，为客户提供全程研发支持。选择三优生物，即意味着选择高效、优质、高成功率的抗体药物研发解决方案，助力创新药物快速转化。展望未来，抗体药物的研发前景无疑是广阔而激动人心的。随着科学技术的不断进步，我们有理由相信，更多创新、高效的抗体药物将不断涌现，为全球患者带来新的希望和更优的治疗选择。三优生物期待与您携手，共同探索抗体药物的无限可能，将更多具有里程碑意义的创新疗法从实验室带到临床，最终惠及每一位需要的患者。Sanyou 10th Anniversary: Service Section Target to PCC Drug Development System Solution01 IntroductionThe legendary journey of antibody drugs began in 1975 with the advent of monoclonal antibody technology, a milestone that revolutionized disease treatment. Over the following decades, breakthroughs in chimeric, humanized, and fully human antibody technologies have continuously accelerated the rapid advancement of this field. Today, more than 170 antibody drugs have been approved worldwide, widely used for major diseases such as cancer and autoimmune disorders. The antibody drug market is experiencing explosive growth, with its share expected to expand further in the coming years. By 2030, it is projected to surpass hundreds of billions of dollars, showcasing a future of immense promise.In the thriving wave of antibody drug development, Sanyou Bio is dedicated to providing clients with one-stop services from target discovery to preclinical candidate (PCC) delivery. Starting with just a target, we deliver high-quality PCC molecules through a comprehensive process covering target research, raw material preparation, molecular discovery & optimization, in vitro/in vivo efficacy evaluation, and druggability analysis. From monoclonal antibodies, bispecific antibodies, to antibody-drug conjugates (ADCs), Sanyou offers customized solutions to accelerate innovative biopharmaceutical R&D. As of now, Sanyou Bio has completed the development of over 60 PCC projects, with more than 10 advancing to clinical stages, including one project in Phase III trials as the fastest progressing candidate.02 Service ProcessSanyou Bio specializes in the field of antibody drug R&D, offering one-stop services covering key stages including target investigation, raw material preparation, molecule generation, in vitro efficacy evaluation, molecule optimization, in vivo efficacy assessment, and druggability analysis. During the R&D process, in-depth target investigation is first conducted to clarify its disease relevance and research value, thereby defining the R&D direction. Subsequently, relevant raw materials—such as antigen proteins and cell lines—are prepared to establish the foundation for further studies. After obtaining candidate molecules based on a trillion-size innovative molecular library, in vitro pharmacological evaluation is conducted to screen for molecules with target activity and optimize their characteristics, in order to further improve their biological activity and drug efficacy. The optimized molecule will undergo in vivo pharmacological validation in animal models, and ultimately its safety, pharmacokinetics, and other key characteristics will be evaluated through comprehensive pharmacokinetic analysis.▲ Fig. 1 Target to PCC drug development flowchart01Target researchTarget identification and validation is a strategically pivotal step bridging basic research and clinical translation throughout the drug discovery pipeline. For addressing unmet clinical needs, target research constitutes the primary phase in innovative antibody drug development. This process systematically evaluates the biological characteristics of target molecules, their molecular mechanisms in disease pathogenesis, as well as current research advances and gaps in relevant fields. By understanding the biological characteristics of targets, distribution variations, and synergistic potential with other therapies, we can establish a complete plan from mechanistic innovation to clinical value translation, ensuring drugs truly focus on 'the right target, the right patient, the right efficacy'. Sanyou Bio has established experienced senior scientist teams across diverse therapeutic areas, including oncology, autoimmune diseases, metabolic disorders, neurological diseases, ophthalmic diseases, cardiovascular diseases, infectious diseases, aging-related diseases, and veterinary therapeutics. The company has completed systematic research on over 300 targets. To date, more than 10 Sanyou-developed programs have advanced to clinical stages via out-licensing, demonstrating the critical value of target profiling.▼ Table. 1 Reported IND project cases02Raw material preparationSanyou Bio has established a comprehensive solution system for raw materials, including plasmids, proteins, mRNA, VLPs, and research cell lines. This platform enables the efficient production of various complex proteins, such as intracellular proteins, membrane proteins, extracellular proteins, as well as specialized targets like GPCRs, ion channels, and cytokines, fully meeting customers' technical demands for challenging protein preparation. Sanyou Bio’s technology platform has achieved industry-leading standards, with an annual production capacity of 100,000 batches of proteins and 1,000 research cell lines. The platform demonstrates exceptional efficiency in raw material preparation: mRNA packaging can be completed in just 18 days; high-quality, QC-approved proteins can be delivered within 2 weeks; and high-expression, high-stability research cell lines are obtainable in just 1 month. The team brings extensive project experience, having successfully completed 500+ milestone or full-service projects, providing robust technical support for antibody development and drug screening.▲ Fig. 2 Raw material preparation solution03Antibody discoverySanyou has established a proprietary, ultra-trillion-scale innovative molecular library with globally leading performance metrics. This library is widely applicable to innovative drug discovery, diagnostic reagent development, detection technologies, and customized research antibodies. The molecular library comprises four major categories: fully human antibodies, single-domain antibodies, animal-derived immune antibodies, and novel molecules. Through 12 technological approaches, it can generate diverse molecular formats, including fully human antibodies, single-domain antibodies, murine monoclonal antibodies, rabbit monoclonal antibodies, bispecific antibodies, polyclonal antibodies, targeting peptides, and small targeting proteins. Integrated with a one-stop high-throughput automated screening platform, this approach significantly shortens the screening cycle and efficiently identifies candidate molecules with high affinity, excellent specificity, and favorable developability. It systematically addresses various molecular development challenges, strongly accelerating drug discovery progress. As of March 2025, the platform has completed screening for 900+ projects, assisted clients in submitting INDs for over 10 projects through co-development or licensing agreements, and filed 115 patent applications globally, with 28 patents granted.▲ Fig. 3 Diversified sources of molecules04In vitro efficacy evaluationIn vitro efficacy screening, as a core component of antibody functional evaluation, significantly accelerates the discovery, screening, and optimization of antibody drugs. Sanyou Bio specializes in innovative antibody drug R&D and has established a stable, efficient, and reliable in vitro efficacy screening platform. The platform currently encompasses modules including flow cytometry analysis, in vitro efficacy method development, sample testing, and non-specific binding detection, ensuring high-efficiency, high-throughput, and high-standard screening of candidate antibodies. The platform has established dozens of multidimensional in vitro efficacy evaluation systems capable of meeting diverse research needs, ranging from antigen-antibody binding and signaling pathway modulation to cellular function assessment. The platform currently offers over 150 project-validated target cell lines, more than 20 project-validated primary cell types, and 51 subcategories of detection methods across 8 major categories, supported by 92 standardized operating procedures (SOPs). Routine assays can be completed within 1 week, while complex assays require up to 4 weeks. Method development takes 2 weeks for standard protocols and 8 weeks for challenging ones.▲ Fig. 4 Solution for in vitropharmacological evaluation05Molecule optimizationSanyou Bio its advanced antibody engineering platform to deliver efficient and specialized antibody optimization services. The platform covers key optimization processes, including humanization, affinity maturation, developability optimization, and half-life extension. It enables precise modifications of functional antibody regions, such as the framework region (FR), complementarity-determining region (CDR), and constant region (Fc).Through refined engineering, Sanyou meets diverse project demands while significantly enhancing antibody performance, including but not limited to:Improved pharmacodynamics & developability、Enhanced cross-reactivity、Refined target specificity、Elimination of potential modification risks. With industry-leading efficiency, Sanyou completes each round of antibody optimization in just 6–8 weeks, accelerating clients' transition to functional screening. Backed by an expert team, the platform has successfully optimized 500+ antibody molecules, with 40+ designed antibodies in regulatory filing and 10+ in clinical trials, demonstrating its reliability and success rate.▲ Fig. 5 Molecular optimization solutions06In vivo efficacy evaluationIn vivo efficacy evaluation, as a critical step in identifying preclinical candidate molecules, further validates their effectiveness and safety in animal models. Sanyou Bio has established a high-throughput, high-quality in vivo efficacy evaluation platform for candidate molecules, encompassing: In vivo efficacy method development system, Animal efficacy evaluation system, Pharmacokinetics (PK) study system, Acute toxicity testing system. This platform focuses on the small and large animal efficacy evaluation market, with a core emphasis on oncology and autoimmune diseases. We have established a comprehensive tumor CDx model system, a non-oncology model platform for autoimmune diseases, as well as cytokine and blood biomarker detection systems. Additionally, we provide complete pharmacokinetic evaluation services from mice to non-human primates, fully meeting preclinical non-GLP research needs.To date, the platform has accumulated over 150 project-validated CDx models, dozens of non-oncology disease models, and more than 40 standard operating procedures (SOPs), successfully supporting over 10 efficacy-related clinical submission projects.▲ Fig. 6 Solution for in vivo drug efficacy evaluation07Developability assessmentAfter years of technological refinement and advancement, Sanyou has established a multidimensional characterization platform covering monoclonal antibodies, polyclonal antibodies, and fusion proteins. The Physicochemical Characterization Platform for antibodies has developed 10 assay items, featuring multidimensional analysis, full compliance, and high-quality efficiency, supporting quality control of early-stage samples in novel biologics development. The Biochemical Analysis Platform has further expanded its testing capabilities through optimized biochemical assay methodologies. ELISA-based biochemical analysis offers advantages including short cycles, high reproducibility, high throughput, and low cost, enabling efficient screening of high-quality candidates from lead molecules and significantly improving "lead molecule focusing" efficiency. This technology has been successfully applied in hundreds of service projects across all R&D stages, from early drug discovery to pilot process development. The platform has established a comprehensive standard system in strict compliance with pharmacopoeia requirements, providing reliable technical support and process guidance for drug manufacturing through accurate characterization methods.▲ Fig.7 Solution for drug analysis03 Service Features01Full process coverageSanyou Bio's Target-to-PCC Drug Discovery Comprehensive Solution covers key stages including target profiling, raw material preparation, molecule discovery, in vitro efficacy evaluation, lead optimization, in vivo efficacy assessment, and developability analysis, ensuring seamless integration across the R&D workflow. This model eliminates efficiency losses caused by inconsistent technical standards, data fragmentation, or communication barriers, enabling precise progression from target identification to PCC development based on prior achievements. Through integrated end-to-end design supported by a unified quality control system and interdisciplinary collaboration, potential risks (e.g., inadequate antibody developability or suboptimal target selectivity) can be identified early, enabling timely strategy adjustment. This approach significantly shortens development timelines, reduces redundant investments, and ultimately improves the success rate of candidate antibodies, providing efficient and reliable technical support for innovative drug development.▲ Fig.8 Full process coverage02Customized adaptationSanyou Bio's Target-to-PCC Drug Discovery System Solution offers customized experimental solutions and technical pathways tailored to target characteristics and project requirements at different R&D stages. This platform dynamically adjusts experimental designs based on developmental phases and client priorities, eliminating resource waste and efficiency loss inherent in standardized workflows. This highly flexible approach ensures precise alignment between research strategies and target biology while focusing on core objectives. It enhances antibody drugability while mitigating late-stage development risks, delivering a more accurate and efficient solution for innovative drug development.▲ Fig.9 Research and statistics on100+ targets of Sanyou Biotechnology03Efficient promotionSanyou Bio's Target-to-PCC Drug Discovery System Solution integrates multiple technology platforms and expert team experience. It accelerates lead molecule screening through AI-assisted design and high-throughput experimental platforms, while ensuring data reliability via stringent quality control systems. This approach enables synchronous resolution of key challenges (activity, selectivity, and druggability) in early stages, reducing late-stage rework risks. Additionally, predictive models built on historical project databases precisely guide experimental direction, significantly shortening the target-to-PCC timeline and mitigating development risks. The solution provides seamless support from early exploration to candidate compound identification.▲ Fig.10 Project operation cycle04 Case Presentation01Development of anti-CTLA4 monoclonal antibodyBasic information：CTLA4 (cytotoxic T-lymphocyte-associated antigen 4, CD152), a member of the immunoglobulin superfamily (IgSF), is a transmembrane protein containing an IgV-like domain in its extracellular region that shares high homology with CD28 (~31% amino acid sequence similarity). Both competitively bind to B7 molecules (CD80/CD86) on antigen-presenting cells (APCs), but CTLA4 exhibits higher affinity (approximately 10-20-fold) and negatively regulates T-cell activation by inhibiting co-stimulatory signals.Distribution condition：CTLA4 is mainly expressed on the surface of activated CD4+/CD8+T cells and regulatory T cells (Tregs), especially in the tumor microenvironment where Tregs highly express CTLA4.Competitive landscape：According to Insight Database, there are currently 139 CTLA4-targeting antibody drugs under development globally, with 5 already marketed and 1 under regulatory review. The first CTLA4 monoclonal antibody approved by the FDA (2011) for melanoma treatment reached a global market size of $1.7 billion in 2020. Tremelimumab is undergoing Phase III clinical trials for cancer and other indications.▲ Fig. 11 Mechanism of action of CTLA402Key results of anti-CTLA4 monoclonal antibody▶ 2.1. Cell level binding activity analysisMost single-domain antibody candidates generated via SanyouBio's molecular discovery platform exhibit favorable cell-binding activity. Fig. 12A demonstrates FACS analysis of candidate antibodies binding to huCTLA-4 CHO cells, showing comparable binding activity to the control antibody. Fig. 12B presents affinity measurement results via FACS analysis against cynoCTLA-4 CHO cells, where the candidate antibodies display similar binding activity relative to the control.▲ Fig. 12 Binding affinity of antibody▶ 2.2. Analysis of blocking activity at the cellular levelFACS was employed to assess whether the candidate antibody blocks the binding of ligands CD80-ECD and CD86-ECD to huCTLA-4 CHO cells. Fig. 13A demonstrates that the candidate antibody effectively blocks CD80-ECD binding to huCTLA-4 CHO cells, with efficacy comparable or superior to the control antibody. Fig. 13B shows that the candidate antibody similarly blocks CD86-ECD binding to huCTLA-4 CHO cells, with blocking efficiency equivalent to or better than the control antibody.▲ Fig. 13 Blocking activity of antibody ▶ 2.3. Cell level binding activity analysis of humanized antibodiesNB25B-17 and NB25gb-1 were humanized using the Trianni Mo™ antibody optimization platform. The binding activities of the obtained sdAbs were evaluated at cellular level. Fig. 14A presents the affinity measurement results of candidate antibodies binding to huCTLA-4 CHO cells by FACS analysis. Fig. 14B shows the affinity measurement results of candidate antibodies binding to cynoCTLA-4 CHO cells by FACS analysis. The results demonstrate that NB25B-17-9-H1-IgG1 and NB25gb-1-11-H1-IgG1 exhibit superior binding capability and cross-reactivity compared to other candidate antibodies.▲ Fig. 14 Binding affinity of antibody▶ 2.4. Analysis of blocking activity at the cellular level of humanized antibodiesFACS was employed to assess whether candidate antibodies block the binding of ligands CD80-ECD and CD86-ECD to huCTLA-4 CHO cells. Fig. 15A demonstrates the blockade of CD80-ECD binding to huCTLA-4 CHO cells by candidate antibodies, while Fig. 15B shows their inhibition of CD86-ECD binding. Results indicate that NB25B-17-9-H1-IgG1, NB25gb-1-11-H1-IgG1, and NB25gb-1-11-H2-IgG1 exhibit superior blocking activity against huCTLA-4 CHO cells compared to the control antibody.▲ Fig. 15 Blocking activity of antibody▶ 2.5. In vivo efficacy evaluationMC38 tumor cells were subcutaneously inoculated into HuCTLA4 mice. When the average tumor volume reached approximately 100 mm³, the mice were randomly divided into four experimental groups: one control group and three treatment groups receiving different antibody doses. The antibody was administered intraperitoneally (twice weekly for three weeks), with treatment concluding on day 32. Anti-CTLA4 antibody administration significantly reduced tumor volume.▲ Fig. 16 In vivo efficacy of antibody05 Summary and OutlookIn the antibody drug development process from target to PCC, Sanyou Bio leverages its ultra-trillion innovative molecule library and integrated R&D platform to successfully complete over 60 target projects (10+ advanced to III clinical stages). With a decade of expertise, Sanyou has established a one-stop, end-to-end service system covering target assessment to PCC delivery, providing comprehensive R&D support. Sanyou provides efficient, high-quality antibody drug solutions with superior success rates, accelerating innovative drug translation.Looking ahead, the future of antibody drug development is undoubtedly vast and exciting. With continuous advancements in science and technology, we are confident that more innovative and highly effective antibody drugs will emerge, offering new hope and better treatment options for patients worldwide. Sanyou Bio looks forward to collaborating with clients globally to explore the boundless potential of antibody therapeutics, translating more landmark innovations from the lab to the clinic, ultimately benefiting every patient in need.推荐阅读三优十周年｜靶点篇-六大恶性肿瘤靶点介绍创新前沿｜2025ADC热门靶点与技术创新启示三优十周年｜AI-STAL篇-千亿高等电点单域抗体库6类分子形式之环状多肽分子产生系统解决方案轻松玩转三优oneClick+线上9大云程序6类分子形式之mRNA分子产生系统解决方案三重好礼相送暨四种抗体制备解决方案全新上线三优生物单域抗体产生系统解决方案三优生物双抗参比品网站SY-BsAb正式上线三优ADC药物研发系统解决方案三优生物oneClick+平台再次上新三优磁阵列全人源小鼠抗体发现平台重磅发布三优超万亿全人单克隆抗体产生平台盘点三优磁阵列全人源小鼠抗体发现平台隆重上线共同轻链抗体产生之超万亿共轻库盘点关于三优生物三优生物是一家以“让天下没有难做的创新生物药”为使命，以超万亿分子库和人工智能技术双驱的生物医药智能高新技术企业。公司以智能超万亿分子库为核心，打造了干湿结合、国际领先的创新生物药临床前智能化及一体化研发平台，通过“新药发现、临床前研究、智能化药物研发及前沿科学研究”等四个维度加速全球新药发现及靶标深度研究。公司总部位于中国上海，在美国、欧洲等地设有子公司，现有投产及布局的研发及GMP场地20000多平方米。公司为合作伙伴提供“差异化CRO、整合型CDO、协同型CPO、特色CRS”于一体的“创新生物药4C综合业务”。公司已建立全球营销网络，已与全球1200多家药企、生技公司等建立了良好的合作关系；已完成了1200多个新药发现及开发服务项目；已完成了50多个合作研发项目，其中9个合作项目已完成临床申报。公司已获得国家高新技术、上海市专精特新、上海市小巨人和上海“张江之星”企业认定。

作者：戴珊珊 周昀茜美工：何国红 罗真真排版：马超01 引言值此三优生物医药十周年之际，我们见证了肿瘤精准医疗的飞速发展。从传统的细胞毒化疗药物到靶向治疗的兴起，从免疫检查点抑制剂的问世到ADC（抗体-药物偶联物）的创新应用，肿瘤治疗正在经历着革命性的变化。本文将聚焦于发病率和致死率相对较高的六大恶性肿瘤——肺癌，乳腺癌、结直肠癌，前列腺癌，胃癌，肝癌，介绍其治疗现状以及在研靶点，为行业专业人士提供全面的靶点开发参考。02 肺癌：精准治疗与免疫革新的前沿阵地肺癌长期位列全球发病率与致死率首位，2022年全球肺癌新发病例248万，死亡182万[1]  。肺癌治疗已进入精准医学时代。目前已形成EGFR/ALK靶向药物、PD-1/PD-L1免疫检查点抑制剂和抗体药物偶联物（ADC）三足鼎立的治疗格局。奥希替尼、帕博利珠单抗等药物显著改善患者生存，而T-DXd、DS-1062等新一代ADC为难治性患者带来新希望[2,3]。在研靶点与创新方向：1）免疫检查点：除PD-1/PD-L1外，CTLA-4、TIGIT、LAG-3等成为联合治疗新选择；2）ADC靶点：C-MET、DLL3、TROP2、CEACAM5、B7-H3等在NSCLC和SCLC中显示显著疗效；3）双特异性抗体：PD-1 × VEGF（ivonescimab）、DLL3 × CD3（tarlatamab）等代表免疫治疗新模式；4）新型靶向药物：KRAS G12C抑制剂等为更多患者提供治疗机会。▲ 图1 基于insight数据库统计肺癌靶点分布图03 乳腺癌：全球女性健康的重大挑战乳腺癌是女性最常见的恶性肿瘤，2022年全球肺癌新发病例229万，死亡67万，预计2040年将增至约300万例[4] 。乳腺癌治疗早期以手术为主，结合新辅助治疗；晚期采用分型指导的全身治疗策略[5] 。治疗模式从单药向精准联合、从晚期向早期辅助延伸。三大亚型展现不同的治疗特点和疗效进展：1）HER2阳性领域，曲妥珠单抗（trastuzumab）仍是核心基础治疗药物，DS-8201等新一代ADC进一步提升了治疗效果[6] ，国产RC48等也显示出良好的疗效[7] ；2）HR+/HER2-领域，CDK4/6抑制剂显著改善了患者生存获益[8] ；3）TNBC领域，TROP2-ADC联合免疫治疗为患者带来治疗突破[9] 。在研靶点与创新方向：1）新型ADC靶点：TROP2、HER3、NECTIN-4、B7-H3、LIV-1等；2）PI3K/AKT通路：alpelisib在PIK3CA突变患者中显效；3）新一代内分泌药物：口服SERD如camizestrant；4）免疫检查点：PD-1/PD-L1、CLTA-4在TNBC中显示潜力；5）表观遗传调节：KMT2C、FOXM1等新靶点。▲ 图2 基于insight数据库统计乳腺癌靶点分布图04 结直肠癌：从传统治疗到精准分子分型结直肠癌是全球第三大高发癌种，仅次于肺癌和乳腺癌。2022年全球新发超190万例，死亡约90万例[1] 。手术切除为早期CRC一线方案，辅助和新辅助化疗根据危险因素分层应用。转移性CRC标准治疗包括基于RAS/BRAF/MSI分型的化疗联合靶向药物（EGFR、VEGF单抗），HER2和BRAF突变亚群也可选择相应靶向。MSI-H/dMMR亚型对免疫检查点抑制剂（PD-1/PD-L1或CTLA-4）响应显著，但仅约5% mCRC患者属于该亚型，其余大多数MSS/pMMR患者对免疫单药疗效有限[10] 。在研靶点与创新方向：1）已上市靶点持续拓展，EGFR、VEGF：EGFR单抗（西妥昔单抗、帕尼单抗）及VEGF单抗（贝伐珠单抗）在RAS/BRAF分型亚组中优化组合，HER2/BRAF靶向药不断纳入新版指南；2）c-MET、CEACAM5、TROP2、CDH17等新兴抗体药物偶联物（ADC）赛道快速推进，部分已进入注册阶段；3）LAG3、TIGIT、CLDN18.2、DLL3、B7-H3等成为双特异性抗体和ADC创新热点，特别是在MSS/pMMR人群联合免疫方向取得进展；4）分层诊疗理念下，mCRC分子分型指导多靶点精准联合（如BRAF/EGFR、HER2/PI3K等新组合），推动生存获益持续提升。▲ 图3 基于insight数据库统计结直肠癌靶点分布图05 前列腺癌：雄激素依赖向个体化精准治疗演进前列腺癌是全球第四大高发癌症，男性第二大恶性肿瘤。2022年前列腺癌新发病例146万，死亡40万人[1,11] 。前列腺癌早期多通过根治性手术和/或放疗治疗。中晚期及转移性病例以内分泌去势（ADT）联合AR抑制剂（阿比特龙、恩扎卢胺等）为标准一线方案，药物耐受性高、副作用相对较轻。去势抵抗后常加用多西他赛等化疗，伴DNA修复缺陷者可用PARP抑制剂奥拉帕利。核素靶向药物、免疫检查点抑制剂、肿瘤疫苗等多线治疗也在逐步应用[12] 。在研靶点与创新方向：1）PSMA：前列腺特异性膜抗原，Lu-177-PSMA-617已获批，多个PSMA-ADC在研；2）AR：雄激素受体仍是核心靶点，新一代AR拮抗剂持续开发；3）GNRHR：促性腺激素释放激素受体，多个激动剂和拮抗剂在研；4）PD-1/PD-L1：免疫检查点，已批准抗体数量最多；5）PARP：聚腺苷二磷酸核糖聚合酶，在BRCA突变患者中显效；6）新兴靶点探索，包括DLL3、STEAP1、TROP2等。▲ 图4 基于insight数据库统计前列腺癌靶点分布图06 胃癌：精准亚型与新靶点带动创新胃癌是全球第五大癌症，2022年全球新发超96万例，死亡约66万例[13] 。胃癌精准治疗格局已基本确立。HER2阳性患者以曲妥珠单抗联合化疗为标准一线治疗[14] ，同时FDA/EMA已批准PD-L1阳性者加用帕博利珠单抗形成三联疗法。德曲妥珠单抗作为新一代HER2-ADC药物，已获批用于二线及后线治疗，显著改善生存获益。2024年12月新上市的佐妥昔单抗成为首个CLDN18.2靶向药物，针对HER2阴性、CLDN18.2阳性患者提供新的治疗选择。在研靶点与创新方向：1）CLDN18.2领域竞争激烈，除已获批的zolbetuximab外，超过100款相关药物在研，包括ADC、双特异性抗体和CAR-T疗法；2）TROP2-ADC领域，sacituzumab tirumotecan等药物展现良好前景；3）新免疫检查点方面，TIGIT抑制剂domvanalimab在EDGE-Gastric研究中显示抗肿瘤活性，STAR221 III期试验正在验证其疗效[13] ；4）新兴靶点探索，包括C-MET、TROP2、MSLN等；5）已上市靶点持续拓展，包括VEGFR2、FGFR2等。▲ 图5 基于insight数据库统计胃癌靶点分布图07 肝癌：免疫组合引领的治疗新格局肝癌是全球第六大癌症和第三大癌症死因，2022年新发病例约90万，死亡病例超过75万，其中中国占全球发病和死亡人数的一半以上，主要危险因素包括乙型肝炎病毒感染、丙型肝炎病毒感染、酒精性肝病和非酒精性脂肪性肝炎。肝细胞癌一线治疗现已步入多元化时代。索拉非尼和仑伐替尼（多靶点TKI）为晚期首选，阿替利珠单抗联合贝伐珠单抗免疫组合（IMbrave150方案）跃升为主要标准。二线包括瑞戈非尼、卡博替尼和拉姆西单抗等TKI，以及免疫检查点抑制剂纳武利尤单抗、帕博利珠单抗。创新药物如靶向VEGF/FGFR的多靶点抑制剂和联合免疫治疗也被广泛应用[15] 。在研靶点与创新方向：1）GPC3成为ADC与CAR-T疗法的重要靶点，已有突破性疗效报道；2）TGF-β通路相关抑制剂（如galunisertib）、TIGIT、LAG-3等新型免疫检查点在持续探索中；3）FGFR4、MET、AXL、PI3K/AKT/mTOR、Wnt/β-catenin等信号轴的新一代小分子抑制剂正在开发；4）肿瘤微环境调控、肠道菌群干预和溶瘤病毒疗法等新方向亦为创新热点[16] 。▲ 图6 基于insight数据库统计肝癌靶点分布图08 总结与展望：协同创新，引领未来肿瘤治疗进入了一个新时代。免疫检查点抑制剂、ADC药物和靶向治疗的快速发展，正在改写多种肿瘤的治疗指南。未来的突破将更多地来自于：◆ 创新靶点的发现：持续挖掘如DLL3、TROP2、B7-H3、GPC3、STEAP1、CDH17等新兴靶点的潜力；◆ 联合用药的智慧：“ADC+免疫”、“双抗+ADC”等联合策略将成为研发主流；◆ 三个体化精准医疗：基于生物标志物的深度分析，为每位患者匹配最优治疗方案。三优生物将继续秉持科学严谨、勇于创新的精神，与全球同道携手，共同推动抗体药物研发，为攻克癌症贡献我们的智慧与力量。注：本文内容基于最新发表的科学文献和临床研究数据，旨在为医药行业专业人士提供参考。具体治疗方案应遵循相关临床指南和专业医师建议。Sanyou 10th Anniversary | Six Major Malignant Tumor Targets Overview01 IntroductionOn the occasion of the 10th anniversary of Sanyou Biopharmaceuticals, we have witnessed the rapid evolution of precision oncology. From traditional cytotoxic chemotherapies to the rise of targeted therapies-and from the advent of immune checkpoint inhibitors to the innovative applications of antibody-drug conjugates (ADCs)-the landscape of cancer treatment is undergoing revolutionary change. This article focuses on high-incidence and high-mortality cancers-lung, breast, colorectal, prostate, and gastric-summarizing the current treatment patterns and landscape of investigational targets, providing industry professionals with a comprehensive reference for target development.02 Lung Cancer: Frontier of Precision Therapy and Immunological RevolutionLung cancer has long ranked first globally in incidence and mortality, with 2.48 million new cases and 1.82 million deaths in 2022[1] . Lung cancer therapy has entered the precision medicine era, now dominated by EGFR/ALK-targeting drugs, PD-1/PD-L1 immune checkpoint inhibitors, and ADCs. Osimertinib and pembrolizumab have significantly improved patient survival, while next-generation ADCs such as T-DXd and DS-1062 offer new hope for refractory cases[2,3] .Emerging Targets & Innovations:(1) Immune checkpoints: In addition to PD-1/PD-L1, new avenues include CTLA-4, TIGIT, LAG-3, enabling combination therapies;(2) ADC targets: C-MET, DLL3, TROP2, CEACAM5, B7-H3 have shown significant efficacy in NSCLC and SCLC;(3) Bispecific antibodies: PD-1×VEGF (ivonescimab), DLL3×CD3 (tarlatamab), representing new models of immunotherapy;(4) Novel targeted drugs: KRAS G12C inhibitors, MET antibodies, HER3-ADC provide more options to patients.▲ Fig.1 Mapping of lung cancer target distribution derived from Insight Database03 Breast Cancer: A Major Challenge to Women’s Health WorldwideBreast cancer is the most common cancer among women, with 2.29 million new cases and 666,103 deaths worldwide in 2022, projected to rise to 3 million cases by 2040[4] . Early-stage treatment emphasizes surgery with neoadjuvant therapy; advanced stages adopt subtype-guided systemic strategies[5] . Treatments have shifted from monotherapy to precise combinations and from late- to early-stage interventions.The three major subtypes demonstrate different treatment characteristics and therapeutic advances:(1) In the HER2-positive domain, trastuzumab remains the core foundational therapy, with next-generation ADCs such as DS-8201 further improving treatment outcomes[6] , while domestic drugs like RC48 also demonstrate good efficacy[7] ;(2) In the HR+/HER2- domain, CDK4/6 inhibitors significantly improve patient survival benefits[8] ;(3) In the TNBC domain, TROP2-ADC combined with immunotherapy brings therapeutic breakthroughs for patients[9] .Emerging Targets & Innovations:(1) Novel ADC targets: TROP2, HER3, NECTIN-4, B7-H3, LIV-1; (2) PI3K/AKT pathway: Alpelisib is effective in PIK3CA mutant patients; (3) Nextgen endocrine drugs: Oral SERD agents such as camizestrant;(4) Immune checkpoints: PD-1/PD-L1, CLTA-4 show promise in TNBC;(5) Epigenetics: KMT2C, FOXM1 and other new targets.▲ Fig.2  Mapping of Breast cancer target distribution derived from Insight Database04 Colorectal Cancer: From Traditional Therapy to Precision Molecular StratificationColorectal cancer is the third most common cancer worldwide, following lung and breast-with over 1.9 million new cases and 904,019 deaths in 2022[1] . Surgical resection remains the mainstay for early CRC, with adjuvant/neoadjuvant chemotherapy applied based on risk stratification. Metastatic CRC is treated with chemotherapy plus targeted drugs (EGFR, VEGF antibodies) guided by RAS/BRAF/MSI subtyping; HER2 and BRAF mutant subsets also have matching options. The MSI-H/dMMR subtype responds well to immune checkpoint inhibitors but accounts for only ~5% of metastatic CRC. Most MSS/pMMR patients show limited benefit from monotherapy[10] .Emerging Targets & Innovations: (1) Extension of existing targets: EGFR and VEGF monoclonal antibodies continue in combination regimens for RAS/BRAF subtypes, with HER2 and BRAF targeting steadily adopted in guidelines;(2) New ADC tracks such as c-MET, CEACAM5, TROP2, CDH17 are progressing rapidly, with some reaching registration phase;(3) Double-specific antibodies and ADCs focusing on LAG3, TIGIT, CLDN18.2, DLL3, B7-H3 are innovative hotspots, especially in combined immunotherapy for MSS/pMMR patients;(4) Under molecular stratification, multi-targeted precise combos (e.g., BRAF/EGFR, HER2/PI3K) continue to push survival benefit upward.▲ Fig.3 Mapping of colorectal cancer target distribution derived from Insight Database05 Prostate Cancer: From Androgen Dependence to Personalized Precision TherapyProstate cancer is the fourth most common cancer globally and the second leading cancer among men, with 1.46 million new cases and 397,430 deaths in 2022[1,11] . Early-stage prostate cancer is primarily treated with radical surgery and/or radiotherapy. Advanced/metastatic cases are treated with androgen deprivation therapy (ADT) plus AR inhibitors (abiraterone, enzalutamide), offering high tolerability and mild side effects. With castration resistance, docetaxel or other chemotherapy and PARP inhibitors (e.g., olaparib) are added where DNA repair defects are present. Radionuclide therapies, immune checkpoint inhibitors, and cancer vaccines are also gradually being adopted[12] .Emerging Targets & Innovations:(1) PSMA: Lu-177-PSMA-617 is approved; several PSMA-ADC drugs are in development;(2) AR: Androgen receptor remains core, with next-gen antagonists under active development;(3) GNRHR: Gonadotropin-releasing hormone receptor agonists/antagonists;(4) PD-1/PD-L1: The most widely approved checkpoint antibodies; (5) PARP: Highly effective in BRCA-mutant cohorts;(6) Exploring novel targets such as DLL3, STEAP1, TROP2.▲ Fig.4 Mapping of Prostate cancer target distribution derived from Insight Database06 Gastric Cancer: Precision Subtyping and Novel Targets Drive InnovationGastric cancer is the fifth most common globally, with over 968,784 new cases and 660,175 deaths in 2022[13] . The standard of care for HER2-positive patients is trastuzumab plus chemotherapy as first-line therapy[14] , with FDA/EMA now approving pembrolizumab for PD-L1-positive patients to form triple combinations. Next-generation HER2-ADC (trastuzumab deruxtecan) is approved for second- and later-line treatment. Zolbetuximab, approved in December 2024, is the first CLDN18.2-targeted therapy for HER2-negative/CLDN18.2-positive patients.Emerging Targets & Innovations:(1) Intense competition in CLDN18.2, with over 100 related agents under development (including ADCs, bispecifics, and CAR-T) besides approved zolbetuximab;(2) TROP2-ADC agents such as sacituzumab tirumotecan show promise;(3) Immune checkpoints: TIGIT inhibitor domvanalimab has shown anti-tumor activity in the EDGE-Gastric trial, with the Phase III STAR221 study ongoing[13] ;(4) New targets such as C-MET, TROP2, and MSLN are under active exploration;(5) Extension of existing targets: VEGFR2, FGFR2.▲ Fig.5 Mapping of Gastric cancer target distribution derived from Insight Database07 Liver Cancer: A New Treatment Paradigm Led by Immune CombinationLiver cancer is the sixth most common and third most deadly cancer worldwide-with about 968,784 new cases and over 758,725 deaths in 2022. Over half of these occur in China, with main risk factors including hepatitis B and C infection, alcoholic liver disease, and non-alcoholic steatohepatitis. First-line therapy for hepatocellular carcinoma is now diverse: sorafenib and lenvatinib (multi-targeted TKIs) as traditional standards for the advanced stage, while the combination of atezolizumab and bevacizumab (IMbrave150) has become a major new standard. Second-line options include regorafenib, cabozantinib, ramucirumab, and immune checkpoint inhibitors (nivolumab, pembrolizumab). Next-generation TKIs targeting VEGF/FGFR and combination immunotherapies are widely used[15] .Emerging Targets & Innovations:(1) GPC3 is a pivotal target for both ADC and CAR-T, with breakthrough efficacy reported;(2) TGF-β pathway inhibitors (like galunisertib), TIGIT, LAG-3 (novel checkpoint targets) are under active exploration;(3) Inhibitors targeting FGFR4, MET, AXL, PI3K/AKT/mTOR, and Wnt/β-catenin pathways are advancing;(4) Tumor microenvironment modulation, gut microbiome intervention, and oncolytic virus therapies are promising new directions[16] .▲ Fig.6 Mapping of Liver cancer target distribution derived from Insight Database08 Conclusion & Outlook: Synergistic Innovation Leading the WayCancer treatment has entered a new era. Immune checkpoint inhibitors, ADCs, and targeted treatments are rapidly rewriting clinical guidelines. Future breakthroughs will increasingly come from:◆ Discovery of innovative targets: Continued exploration of new targets such as Claudin 18.2, TROP2, B7-H3, and CDH17;◆ Combination wisdom: Strategies such as “ADC plus immunotherapy” and “bispecific plus ADC” will become R&D mainstream;◆ Personalized precision medicine: Deep biomarker analysis enables optimal treatment for each patient.SanyouBio will continue to uphold scientific rigor and innovative spirit, working in concert with global peers to advance antibody drug development and contribute our wisdom and strength to conquering cancer.Note: This content is based on the latest published scientific literature and clinical research data, and is intended as a reference for medical industry professionals only. Specific treatment decisions should follow current clinical guidelines and the recommendations of professional physicians.▍参考文献[1] BRAY F, LAVERSANNE M, SUNG H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J/OL]. CA: A Cancer Journal for Clinicians, 2024, 74(3): 229-263. DOI:10.3322/caac.21834.[2] ZHAO S, ZHAO H, YANG W, et al. The next generation of immunotherapies for lung cancers[J/OL]. Nature Reviews Clinical Oncology, 2025: 1-25. DOI:10.1038/s41571-025-01035-9.[3] ZHOU F, GUO H, XIA Y, et al. The changing treatment landscape of EGFR-mutant non-small-cell lung cancer[J/OL]. Nature Reviews Clinical Oncology, 2025, 22(2): 95-116. DOI:10.1038/s41571-024-00971-2.[4] ARNOLD M, MORGAN E, RUMGAY H, et al. Current and future burden of breast cancer: Global statistics for 2020 and 2040[J/OL]. The Breast, 2022, 66: 15-23. DOI:10.1016/j.breast.2022.08.010.[5] GRADISHAR W J, MORAN M S, ABRAHAM J, et al. Breast Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology[J/OL]. Journal of the National Comprehensive Cancer Network, 2024, 22(5): 331-357. 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