作者: Tamot, Ninkka ; Patwardhan, Gauri Anand ; Mazzanti, Nicholas ; Francese, Andrea ; Luo, Jinquan ; Sukumar, Madhusudhanan ; Sum, Chi Shing ; Plummer, Joseph ; Ports, Michael ; Rossillo, Julie ; Borrok, M. Jack ; Spiller, Kara L.

Chimeric antigen receptor (CAR)-modified T cells have garnered substantial attention due to their clinical success, culminating in six Food and Drug Administration-approved therapies for hematological malignancies. Notably, CD19-specific CAR T cell therapies have achieved remarkable clinical efficacy in treating B-cell malignancies, but these profound and durable responses are not observed in CAR T therapies targeting other indications, particularly solid tumors. Key design elements of CAR constructs - namely, antigen binding affinity and spacer length - play critical roles in determining T cell effector function and overall therapeutic effectiveness. Refining CAR designs may enhance T cell functionality, extend clinical application, and potentially apply CAR T cell therapies across a wider array of malignancies. In this study, affinity variant and spacer variant CARs targeting BCMA and DLL3 tumor antigens were evaluated using in vitro measurements of antigen-binding properties and effector function. Each panel of CARs spanned 2-3 logs of antigen binding affinity (BCMA: 181 pM KD to 74 nM KD, DLL3: 417 pM to 407 nM). Additionally, CAR T cells were challenged with tumor spheroids composed of BCMA⁺ H929 and DLL3⁺ SHP77 tumor cells. We show that for both tumor models, higher affinity CARs (KD stronger than approximately 100 nM) paired with an intermediate length spacer (IgG1 Fc, CH2-CH3, 230AA) elicited the strongest levels of tumor killing, CAR⁺ T cell expansion, and proinflammatory cytokine production. These CARs displayed the strongest cellular affinity when measured in a conjugation assay, suggesting a relationship between cellular affinity and T cell functional performance. This study highlights the critical role of CAR design in enhancing T cell functionality, demonstrating that high-affinity CARs combined with intermediate-length spacers yield superior performance in targeting BCMA and DLL3 antigens. This study provides a framework for rational CAR design, informing strategies to broaden the clinical utility of CAR T-cell therapies beyond hematologic cancers.

2026-07-01·EUROPEAN JOURNAL OF HAEMATOLOGY

Elranatamab in Relapsed/Refractory Multiple Myeloma: Mechanisms, Clinical Evidence, and Emerging Perspectives

Review

作者: Santino Caserta ; Massimo Gentile ; Eugenio Lucia ; Virginia Olivito ; Francesco Mendicino ; Ernesto Vigna ; Enrica Antonia Martino ; Caterina Labanca ; Nicola Amodio ; Maria Eugenia Alvaro ; Mamdouh Skafi ; Fortunato Morabito ; Antonella Bruzzese

ABSTRACT:

Relapsed and refractory multiple myeloma (RRMM) remains associated with poor outcomes, particularly in patients exposed or refractory to proteasome inhibitors, immunomodulatory agents, and anti‐CD38 monoclonal antibodies. Targeting B‐cell maturation antigen (BCMA) has emerged as an effective therapeutic strategy, prompting the development of bispecific antibodies that redirect T‐cell cytotoxicity toward malignant plasma cells. Elranatamab is a humanized BCMA × CD3 bispecific antibody that has demonstrated clinically meaningful activity in heavily pretreated RRMM. This review summarizes and critically appraises available evidence on elranatamab, focusing on its mechanism of action, clinical efficacy, safety profile, patient‐reported outcomes, and comparative positioning within the evolving BCMA‐directed treatment landscape. Across studies, elranatamab has shown high response rates, durable disease control, and manageable toxicity, with predominantly low‐grade cytokine release syndrome and limited neurotoxicity when administered with step‐up dosing. Emerging data indicate preserved efficacy in patients previously exposed to BCMA‐targeted therapies and feasibility in selected high‐risk populations, including those with severe renal impairment. Nevertheless, uncertainties remain regarding optimal sequencing, long‐term survival benefit, infection risk management, and mechanisms of resistance. Overall, elranatamab represents a valuable addition to the therapeutic armamentarium for RRMM. Ongoing studies and real‐world experience will be critical to refine its positioning, identify patients most likely to benefit, and define its role in combination strategies.

2026-06-01·EJHaem

BCMA CAR T for AL Amyloidosis After Plasmacytic Relapse of Lymphoplasmacytic Lymphoma

Article

作者: Brailovski, Eugene ; Rosenzweig, Michael ; Cook, Melinda ; Dela‐Pena, Jacqueline ; Al Haddad, Nadia ; Jolie Landau, Heather

ABSTRACT:

Introduction:

Lambda immunoglobulin light chain (AL) amyloidosis associated with non‐IgM lymphoplasmacytic lymphoma (LPL) is rare and often refractory to conventional therapies. Treatment options for relapsed disease remain limited.

Methods:

Here we describe the case of a patient with a history of LPL‐associated AL amyloidosis who had previously been treated with multiple B‐cell‐ and plasma‐cell‐directed regimens. At the time of relapse, pathology demonstrated plasmacytic histology, with BCMA‐expressing plasma cells by immunohistochemistry and no detectable B‐cell infiltrate. The patient subsequently received investigational B‐cell maturation antigen (BCMA)‐directed chimeric antigen receptor (CAR) T‐cell therapy.

Results:

Following BCMA‐directed CAR T‐cell therapy, the patient achieved a complete hematologic response.

Conclusion:

This case highlights the biologic complexity of LPL‐associated AL amyloidosis and supports the use of BCMA‐targeted therapy, especially when the relapsing or residual disease is comprised by the plasma cell component.

Trial Registration:

ClinicalTrials.gov identifier: NCT06097832.

项与 BCMA(Abzyme Therapeutics) 相关的新闻（医药）

2026-07-15

·罕见希望

多种生物制剂失败，双靶点通用型CAR-T会是溃疡性结肠炎和克罗恩病的答案吗？

点击蓝字关注我们溃疡性结肠炎（UC）和克罗恩病（CD）统称为炎症性肠病（IBD），是一类病因尚不明确的慢性、复发性肠道炎症性疾病。过去二十年来，生物制剂的问世确实改变了IBD的治疗格局。从抗TNF-α单抗到抗整合素抗体、抗IL抗体，越来越多的生物制剂为患者提供了更多选择。然而，现实远比理想复杂。相当比例的患者对生物制剂存在原发性或继发性失应答，即要么一开始就无效，要么用着用着就失效了。具体表现为：部分患者出现原发性失应答，首次使用生物制剂就无效；另一些患者则出现继发性失应答，初期有效但后续疗效逐渐丧失，甚至产生特异性抗药抗体。即便换用另一种生物制剂，仍有相当比例的患者无法获得持续缓解。对于已经使用过2种或以上生物制剂仍然处于中重度活动期的UC和CD患者来说，治疗选择正变得越来越少。反复发作的腹痛、腹泻、便血严重影响日常生活，长期使用激素和免疫抑制剂带来的副作用也让人不堪重负。这类患者，正是医学界常说的 “难治性IBD”人群——他们最需要新的治疗突破。 CAR-T细胞疗法：从肿瘤治疗到自身免疫性疾病那么，当多条生物制剂治疗通路都走不通时，还有别的路吗？近年来，一种名为嵌合抗原受体T细胞（CAR-T）的疗法，正从血液肿瘤治疗领域拓展到自身免疫性疾病的战场。简单来说，CAR-T疗法的工作原理是：从人体内提取免疫系统中的“战士”——T细胞，通过基因工程技术为这些T细胞装上能够精准识别特定靶点的“导航系统”（即嵌合抗原受体，CAR），然后将改造后的CAR-T细胞回输到患者体内，让它们精准找到并清除致病细胞。在肿瘤领域，CAR-T疗法已在某些血液肿瘤中取得了较高的完全缓解率。而近年来，这一技术在系统性红斑狼疮（SLE）等B细胞驱动的自身免疫性疾病中也取得了突破性进展。2025年，德国埃尔朗根大学医院团队成功报道了一位21岁的难治性溃疡性结肠炎患者接受CD19 CAR-T治疗的案例，相关成果发表于《新英格兰医学杂志（NEJM）》。这位患者此前已对所有可用药物（包括多种生物制剂和JAK抑制剂）耐药。CAR-T治疗后，患者的腹泻和腹痛显著改善，肠镜检查显示之前发炎的肠道黏膜实现愈合。这一案例提示，CD19 CAR-T细胞治疗有望为难治性UC患者带来新的治疗可能。需要强调的是，CAR-T细胞治疗炎症性肠病仍处于早期临床探索阶段，上述案例仅为个例报道，其长期疗效和安全性仍需更多临床研究验证。靶向CD19/BCMA的双靶点设计：更彻底的“免疫重置” 传统的CD19 CAR-T主要靶向CD19⁺B细胞，但研究发现，部分致病性抗体可能来源于CD19⁻BCMA⁺的长寿浆细胞——这类细胞可以逃避单纯CD19靶向的清除。正是基于这一科学发现，靶向CD19和BCMA的双靶点CAR-T应运而生。CD19是B细胞表面的标志物，而BCMA则主要表达在更成熟的浆细胞表面。通过同时靶向这两个靶点，双靶点CAR-T可以同步清除CD19⁺和BCMA⁺的致病细胞，实现比单靶点更深、更持久的缓解。临床前和早期数据表明，双靶点策略能更有效地清除致病性免疫细胞，使患者获得更深层次的缓解。此外，与传统需要为每位患者单独制备的 “自体CAR-T” 不同，“通用型CAR-T” （又称“现货型”）是利用健康供体的T细胞进行改造，实现规模化生产和“现货”供应。这意味着患者不需要等待数周的制作周期，治疗可及性有所提高。为何建议生物制剂效果不佳的患者了解CAR-T细胞治疗？综合以上信息，对于已经尝试过2种或以上生物制剂但仍处于中重度活动期的UC和CD患者，CAR-T细胞治疗之所以值得关注，主要基于以下几点：第一，作用机制的根本不同。生物制剂是通过阻断特定的炎症通路（如TNF-α、IL等）来“抑制”炎症。而CAR-T则是通过清除产生致病性抗体的B细胞，从根源上“重置”免疫系统。第二，为耐药患者提供新出路。对于已经对多种生物制剂耐药的患者，传统治疗路径已基本走到尽头。CAR-T作为一种全新机制的疗法，不受既往生物制剂耐药机制的影响，为这部分患者提供了新的治疗选择方向。第三，双靶点设计实现更深度清除。靶向CD19/BCMA的双靶点设计，理论上可以更全面、更彻底地清除致病性B细胞，包括那些可能逃避单一靶点的长寿命浆细胞。第四，“通用型”提升可及性。 “现货”供应意味着患者无需经历漫长的细胞制备等待期，治疗更加便捷。当然，需要清醒地认识到，CAR-T细胞治疗IBD仍处于早期临床探索阶段。目前已有初步的案例报道和积极的早期数据，但其长期疗效、安全性和最佳适用人群仍需更多临床研究来验证。一项正在进行的临床研究正是基于上述科学背景和临床需求，目前有一项针对既往用过2种或以上生物制剂仍在活动期的中重度溃疡性结肠炎和中重度克罗恩病患者的临床研究正在开展。该项研究由武汉三甲医院牵头，旨在探索一种新型靶向CD19/BCMA的双靶点通用型CAR-T细胞疗法，治疗炎症性肠病的安全性、有效性及药代动力学。研究已获得医院伦理委员会批准。如果您或您的家人正面临以下情况：年龄在18至70周岁之间已确诊为溃疡性结肠炎或克罗恩病对至少2种不同机制的生物制剂存在疗效不佳、疗效丧失或耐受性不良目前仍处于中重度活动期那么，您可能有机会参与到这项前沿的临床研究中来。中重度活动性溃疡性结肠炎、克罗恩病临床新药，免费申请入排重点 ✅年龄在18至70周岁之间 ✅已确诊为溃疡性结肠炎或克罗恩病 ✅对至少2种不同机制的生物制剂存在疗效不佳、疗效丧失或耐受性不良 ✅目前仍处于中重度活动期患者权益 1、免费用上全球前沿的双靶点CAR-T细胞免疫疗法，无需承担高昂的细胞制备与治疗费用； 2、免费提供研究所需的内镜检查、血液检测、影像学检查、免疫指标监测等全套评估项目；3、由三甲医院消化科、细胞治疗专业团队全程诊疗、定期随访，精准把控病情变化；4、有望摆脱长期服药、反复复发的困境，实现肠道黏膜愈合，达到长期临床缓解，显著提升生活质量。5、一定的交通补助资料提报 1、3个月前确诊病历、病理或内镜检查报告。2、既往的用药医嘱、用药凭证。 3、既往其他病史及用药情况收集。4、近期血象、血生化收集（如有）研究城市省份城市湖北省武汉市如果你对CD19/BCMA的双靶点通用型CAR-T治疗或相关临床项目感兴趣，欢迎扫码添加我的微信，我将为你提供详细资讯和专业解答。长按扫描二维码添加微信了解更多罕见病临床试验资讯治疗之路或许漫长，但请相信——数据在说话，科学在进步，希望从未缺席。你并不孤单。 END 版权声明 | 本文信息来源互联网，由罕见希望整理编辑。如有侵权，请联系管理员删除。免责声明 |本文仅为前沿医学资讯科普分享，不构成任何疾病诊断、用药指导及医疗治疗建议，所有患者的诊疗方案请严格遵从肾内科专科医师指导。在研临床试验药物，尚未获批上市，其临床疗效与安全性仍处于临床试验验证阶段。本文提及的相关研究数据均来源于公开学术资料，个体获益存在差异化，不代表所有受试者均可获得同等临床效果。临床试验招募仅作信息科普，最终入组资格需由研究医生结合完整病历、检查报告综合评估，严格以官方试验方案入排标准为准。点个"赞"再走吧~

2026-07-13

·研日新

研日新日报 ·3| 07月13日全科医学 | 血液内科 | 皮肤科

日报精选医学文献今日精选20篇医学文献，查看更多请点击阅读原文本文支持继续浏览摘要内容；完整摘要、收藏文章、订阅管理等完整功能，请前往小程序「医研日新」。前往小程序查看更多与订阅收藏 1. Hospitalizations and deaths from major respiratory viruses in the US: An ensemble time series modeling study, 2016-2025. [COVID-19] The Journal of infection | 2026-07-11 | IF 14.3 AISARS-CoV-2已成为美国呼吸道病毒相关住院和死亡的重要驱动因素，接种流感疫苗和RSV疫苗仍是降低高危人群疾病负担的关键干预措施。摘要To estimate the hospitalization and mortality impact of influenza, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), rhino/enteroviruses (RV/EV), and SARS-CoV-2. We applied age-specific time series regression models to weekly vital statistics and medical claims data for inpatient hospitalizations from the United States (US) from 2016 to 2025. Our results represent probabilistic esti...查看完整摘要 2. Christensenella massiliensis reduces kynurenine levels and alleviates obesity and related metabolic disorders in model mice. [Obesity] Gut microbes | 2026-07-11 | IF 12.2 AIC. massiliensis通过调节肠道激素和代谢犬尿氨酸改善肥胖相关代谢紊乱，为开发针对代谢综合征的活体生物药提供了临床前证据支持。摘要Next-generation probiotics derived from gut commensals show promise for metabolic disease intervention, yet effective anti-obesity strains remain limited. Here, we demonstrate that oral administration of Christensenella massiliensis markedly alleviates obesity and metabolic dysfunction in high-fat diet-induced obese mice. Treatment reduced food intake, improved glucose tolerance and insulin...查看完整摘要 3. Epidemiology of Alcohol-Associated Hepatitis: A Systematic Review of Population-Based Studies. [COVID-19] 综述 | Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | 2026-07-11 | IF 11.6 AI临床医生应认识到酒精相关性肝炎发病率呈全球性上升趋势，尤其需关注大流行期间及之后的发病率变化，并积极采用标准化诊断标准以准确识别和报告病例。摘要Alcohol-associated hepatitis (AH) is an acute and severe manifestation of alcohol-related liver injury that can occur at any stage of fibrosis. Despite its high mortality, reliable epidemiological data on AH remain limited. We conducted a systematic review to synthesize available population-based estimates of AH annual incidence and point prevalence from 2000 to 2025. A comprehensive literature se...查看完整摘要 4. Integrating Policies that Enable Minimally Processed Foods with Policies that Restrict Ultra-Processed Foods for Obesity and Noncommunicable Disease Prevention. [Obesity] 综述 | Current obesity reports | 2026-07-11 | IF 11.0 AI临床医生在慢病预防中应超越个体行为干预视角，关注系统性食品政策对人群饮食模式的影响，将政策信息整合至患者营养教育策略中。摘要Historically, many food policies for obesity and noncommunicable disease prevention focus on reducing the demand for ultra-processed foods (UPFs). This narrative review examines why integrating policies that enable minimally processed foods (MPFs) with UPF restriction is critical for improving diets and health. Despite progress from UPF-restrictive policies, MPF-related barriers like limited avail...查看完整摘要 5. Neurobiological subtypes in alcohol use disorder and their phenotypic and clinical profiles. [Alcoholism] Molecular psychiatry | 2026-07-11 | IF 9.6 AIAUD患者可依据神经影像标志物划分为两种亚型，其行为特征（外部化vs内部化）比症状严重程度更具区分度，有助于实现基于神经生物学的个性化治疗分配。摘要Alcohol Use Disorder (AUD) is associated with vast clinical, behavioral, and neurobiological heterogeneity that hinder both the efficacy of current interventions and future treatment development. While recent efforts have focused on stratifying psychiatric disorders based on underlying neurobiological markers, such approaches remain largely unexplored in AUD. To address this, we empirically-derive...查看完整摘要 6. The efficacy, safety, and rationale of orelabrutinib combined with obinutuzumab (O2) as a first-line systemic treatment for marginal zone lymphoma. [Lymphoma] 信函 | Blood cancer journal | 2026-07-11 | IF 12.9 AIO2无化疗方案为边缘区淋巴瘤一线治疗提供了新的选择，BTK抑制剂与抗CD20单抗的协同机制可能在保证疗效的同时改善患者耐受性。 7. Dermatological manifestations associated with chemsex. [Mucositis] 综述 | Journal of the European Academy of Dermatology and Venereology : JEADV | 2026-07-11 | IF 8.4 AI皮肤科医师应熟悉化学性行为相关特征性皮损，以便在诊疗中早期识别高危人群，提供非污名化的风险干预和转诊建议。摘要Chemsex involves the use of psychoactive substances to facilitate or enhance sexual activity, particularly among gay, bisexual, and other men who have sex with men (GBMSM). Common substances used include methamphetamine, gamma-hydroxybutyric acid/gamma-butyrolactone (GHB/GBL), mephedrone, ketamine, inhaled nitrites ('poppers'), and cocaine, all of which are linked to various dermatological complic...查看完整摘要 8. Metabolic and functional analysis including repetitive antigen stimulation provides a more accurate assessment for CAR-T cell product quality and long-term functionality. [Multiple Myeloma] Journal of translational medicine | 2026-07-11 | IF 6.1 AICAR-T细胞产品代谢特征与临床疗效密切相关，代谢分析可作为预测长期治疗效果的重要工具，建议临床医生在产品选择时关注代谢功能指标。摘要BCMA-directed CAR-T cell therapy has demonstrated remarkable clinical efficacy in multiple myeloma, but robust methods to evaluate product quality and predict long-term functionality remain underdeveloped. While immunophenotypic features of leukapheresis products correlate with clinical outcomes, the characterization of infused CAR-T cell products remains challenging and inconsistent across studie...查看完整摘要 9. Dual-targeting LILRB3/LILRB4 CAR-T cells for the treatment of monocytic acute myeloid leukemia. [Leukemia] Biochemical pharmacology | 2026-07-11 | IF 5.3 AI双靶向LILRB3/4 CAR-T细胞在保留正常造血功能的同时，可有效清除单核细胞性AML细胞系和原代白血病细胞，为复发/难治性单核细胞性AML患者提供了新的精准治疗选择。摘要Monocytic acute myeloid leukemia (AML) is an aggressive malignancy associated with poor prognosis. High expression levels of LILRB3 and LILRB4 are commonly observed in monocytic AML. In this study, the expression of LILRB3 and LILRB4 was analyzed in monocytic AML patient samples, leukemic stem cell-enriched populations, and AML cell lines, revealing frequent co-expression and suggesting that a dua...查看完整摘要 10. Combined therapy with ALK inhibitors and a novel EGFR-targeting antibody‒drug conjugate as a strategy for ALK-rearranged non-small cell lung cancers. [Lymphoma] Oncogenesis | 2026-07-10 | IF 5.9 AI对于ALK重排且EGFR高表达的NSCLC患者，ALK抑制剂联合EGFR靶向ADC可能成为克服耐药的新策略，在不增加毒性的前提下提升疗效。摘要Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death. Targeted monotherapies against the actionable oncogenic drivers, including anaplastic lymphoma kinase (ALK) rearrangement and epidermal growth factor receptor (EGFR) dysregulation, are well-established for molecularly selected NSCLC patients. However, therapeutic resistance remains a major clinical challenge, and...查看完整摘要 11. Cancer history and second cancer risk in polycythemia vera and essential thrombocythemia. [Melanoma] Blood cancer journal | 2026-07-11 | IF 12.9 AI对于PV和ET患者，既往癌症病史是发生第二原发癌的强预测因素，尤其是既往非黑色素瘤皮肤癌患者后续发生皮肤癌的风险显著增高（6倍以上），提示该人群需要进行个体化的强化癌症监测策略。摘要Patients with myeloproliferative neoplasms (MPN), including polycythemia vera (PV) and essential thrombocythemia (ET), have an increased risk of second cancers (SC), although determinants of risk remain incompletely defined. We retrospectively analyzed 1968 consecutive patients with PV or ET (median follow-up 11.2 years) to identify predictors of SC. Cumulative incidence functions were estimated u...查看完整摘要 12. Wireless Microneedle Patch with Integrated Electrochemical Sensor for In Situ Detection of Melanoma Biomarker Tyrosinase in ISF. [Melanoma] Analytical chemistry | 2026-07-11 | IF 6.7 AI该无线微针平台可无创连续监测皮肤酪氨酸酶水平，为黑色素瘤早期筛查和病情随访提供了一种便捷、定量的新工具。摘要Wearable microneedle biosensors have garnered significant attention for in situ analysis of biomarkers in interstitial fluid (ISF), providing a minimally invasive approach for continuous health monitoring. Nevertheless, there has been little advancement in the field of cancer diagnostics, especially in the early diagnosis of skin cancer. Here, we introduce a wearable microneedle patch with integra...查看完整摘要 13. Clinical and genetic characterization of genital and inverse psoriasis as a distinct psoriasis endotype. [Psoriasis] The Journal of investigative dermatology | 2026-07-11 | IF 5.7 AI生殖器及反向型银屑病可能代表一类独立于经典斑块型银屑病的独特表型，遗传学特征差异有助于临床精准分型和个体化治疗决策。 14. Association Between Household Endotoxin Exposure and Atopic Dermatitis: A Cross-Sectional U.S.-Based Population Study. [Eczema] The Journal of investigative dermatology | 2026-07-11 | IF 5.7 AI请提供完整摘要内容以便进行翻译和关键信息提炼。 15. PRMT5 promotes psoriatic inflammation through mediating dimethylation of p65 in keratinocytes. [Psoriasis] Molecular medicine (Cambridge, Mass.) | 2026-07-10 | IF 6.0 AIPRMT5抑制剂（EPZ015666）有望成为银屑病新型治疗药物，通过阻断p65二甲基化稳定化来抑制NF-κB介导的炎症反应。摘要Psoriasis is a chronic inflammatory skin disease driven by aberrant keratinocyte activation and immune dysregulation. Protein arginine methyltransferase 5 (PRMT5) was identified as a candidate regulator in psoriatic keratinocytes, yet its function and mechanistic role in psoriasis pathogenesis remain unclear. We analyzed multiple public bulk RNA-sequencing and single-cell RNA-sequencing (scRNA-seq...查看完整摘要 16. Reporting of antibiotic resistance in randomized controlled trials of new antibiotics: a systematic review. [Bacterial Infections] 综述 | Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases | 2026-07-11 | IF 10.9 AI该研究揭示当前抗生素临床试验中耐药性评估严重不足，仅少数试验完整报告所有耐药领域，提示临床医生在解读新型抗生素疗效证据时应关注耐药分层数据的报告质量。摘要Planning and reporting of antibiotic resistance at baseline and as an outcome in randomized controlled trials (RCTs) of new antibiotics is important for trial interpretation. To assess the planning and reporting of antibiotic susceptibility testing (AST) in recent randomized controlled trials of new antibiotics. Data sources: MEDLINE, EMBASE, Web of Science, Cochrane Central, and Ai2 Paper Finder ...查看完整摘要 17. Which trial do we need? Treatment of severe measles. [Measles] Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases | 2026-07-11 | IF 10.9 AI重症麻疹治疗缺乏高质量循证证据，亟需设计良好的临床试验来验证维生素A、免疫调节及支持治疗的疗效，为改善患者预后提供科学依据。 18. Hydrogel-based platforms for localized cancer treatment: Design strategies for precision therapeutic delivery. [Carcinoma] 综述 | Journal of controlled release : official journal of the Controlled Release Society | 2026-07-11 | IF 10.5 AI水凝胶平台通过局部缓释和肿瘤微环境响应特性，有望替代传统系统性化疗，在提高抗肿瘤疗效的同时显著降低全身毒副作用。摘要Cancer remains a leading cause of global mortality, with over 1.2 million cancer related death estimated for 2026 in EU alone. Although advances in chemotherapy and immunotherapy have improved cancer treatment, systemic administration of these agents often results in severe off-target toxicity and limited efficacy, due to rapid clearance and poor tumor penetration. This review examines the pivotal...查看完整摘要 19. Periodic surveillance of intraductal papillary mucinous neoplasms: gaps in evidence and future directions. [Pancreatic Cyst] Journal of the National Cancer Institute | 2026-07-11 | IF 9.9 AI当前IPMN监测缺乏统一标准，临床医生应结合多指南建议进行个体化评估，同时关注新兴风险分层工具以优化监测决策。摘要Intraductal papillary mucinous neoplasm (IPMN) is a well-established precursor to pancreatic cancer; however, its generally indolent biological behavior necessitates prolonged periodic surveillance in most patients. This review synthesizes current evidence and highlights unmet needs, while providing future perspectives on the clinical management of patients with IPMNs. In contrast to the relativel...查看完整摘要 20. CSF and plasma tau biomarkers in the Down syndrome-Alzheimer's disease continuum. [Dementia] EBioMedicine | 2026-07-11 | IF 9.7 AI血浆p-tau217在追踪唐氏综合征相关阿尔茨海默病进展中兼具早期敏感性和症状期动态监测优势，可用于指导该高危人群的疾病分期和临床监测。摘要Nearly all individuals with Down syndrome (DS) develop Alzheimer's disease (AD) dementia, primarily due to overexpression of the APP gene. Although specific cerebrospinal fluid (CSF) and plasma tau biomarkers have been investigated in DS-AD, how different tau species change in the DS-AD continuum in comparison to sporadic AD remains uncertain. In this cross-sectional study, we analysed CSF and pla...查看完整摘要在小程序获取完整功能收藏文章、管理订阅、查看本期完整摘要与个性化内容，请前往小程序「医研日新」。前往小程序查看更多内容免责声明：仅供学术交流参考，不构成任何医学建议或诊疗指导

2026-07-03

·国际干细胞与免疫细胞研究

全国首张实体瘤CAR-T处方落地北京！99万一针换2.43个月生存期，到底值不值？

点击蓝字关注我们 2026年6月22日，全球首款实体瘤CAR-T疗法舒瑞基奥仑赛（恺力美®）正式获批上市，专门针对Claudin18.2阳性晚期胃癌、胃食管结合部腺癌。获批仅隔一天，6月23日，全国首张临床处方在北京开出，宣告实体瘤治疗正式进入CAR-T时代！可这份里程碑式的医学突破，却伴随着巨大的行业与大众争议：99万元全额自费的天价治疗费用，搭配有限的生存获益，让全网陷入热议——这针天价CAR-T，究竟是晚期患者绝境翻盘的救命新希望，还是性价比极低的医疗“奢侈品”？一张处方，撕开晚期胃癌的两难现实这张具有里程碑意义的处方，背后是一位57岁晚期胃癌患者的真实绝境与挣扎。患者确诊胃体、胃窦低黏附性腺癌，伴随预后极差的腹膜转移，在完成标准二线治疗后，肿瘤依旧持续进展，彻底耐药。此时化疗无效、无合适靶向药、常规免疫治疗也无法开展，临床已无标准救治方案，属于典型的终末期难治胃癌。就在几乎无路可走的时刻，她的病理报告出现了唯一的生机：Claudin18.2阳性高达90%，完美匹配全新实体瘤CAR-T疗法。一边是绝境里唯一的救命新方案，一边是普通家庭难以承受的99万自费费用，强烈的落差赤裸裸撕开了晚期胃癌创新治疗最真实、最残酷的两难现实，，也让无数家属陷入两难抉择。读懂2.43个月：别单看数字，看清晚期胃癌的治疗基线，理性看待细胞疗法进展，从来不止“延长生命”这一个答案大众争议的核心，集中在“99万仅延长2.43个月生存期”，但我们必须把数据放回多线治疗失败的晚期胃癌这个特殊人群中客观解读。这类患者常规后线治疗疗效极度低迷，传统方案客观缓解率仅4%，疾病控制率不足30%，中位总生存期普遍不足6个月，可供选择的有效治疗手段寥寥无几。2.43个月的生存延长，是在极低生存基线上争取到的宝贵窗口，部分患者还能实现肿瘤缩小、腹痛腹水等晚期症状大幅缓解，甚至等到后续新药、临床试验机会。支撑药物获批的是全球首个实体瘤CAR-T随机对照Ⅱ期临床试验（NCT04581473）的振奋数据，156例二线以上进展、Claudin18.2阳性患者按2:1分组对比，完整数据发表于《柳叶刀》、2026 ASCO大会公开： 1、意向治疗全人群：舒瑞基奥仑赛（satri-cel）组中位总生存期（mOS）7.92个月，传统方案组5.49个月，生存期提升超30%；无进展生存期（mPFS）3.25个月，远高于对照组1.77个月，肿瘤进展风险下降63%。 ▲图源“carsgen”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 2、完成给药有效人群：satri-cel组中位总生存期（mOS）达8.61个月；对照组仅5.49个月，生存获益差距进一步拉大。 3、交叉治疗验证：传统方案进展后换用satri-cel，患者中位总生存期可达9.20个月；全程仅接受常规治疗的患者，中位OS仅3.98个月。 ▲图源“carsgen”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 NEXT 《柳叶刀》还刊登过一组典型病例，能直观体现这款疗法的远期潜力：有患者输注舒瑞基奥仑赛第2周肝脏病灶出现暂时性增大（免疫治疗常见假性进展），持续随访下病灶逐步退缩，至第26周时病灶体积已低于治疗基线，印证CAR-T存在延迟起效的特点。 ▲图源“The Lancet”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除综上，疗效对比综合来看，舒瑞基奥仑赛直接将客观缓解率（ORR）提升至22%，是传统后线治疗的5倍；试验队列中已有2名患者依靠该疗法实现近5年长期无病生存，打破晚期胃癌生存期极短的固有困境。 CAR-T十年攻坚：从血液瘤明星，首次攻克实体瘤难关过去十年，CAR-T细胞疗法在白血病、淋巴瘤等血液肿瘤中收获亮眼成果，早已成为成熟临床方案。但面对胃癌、胰腺癌这类实体瘤，它长期举步维艰。实体瘤会构建封闭、强抑制的“免疫荒漠微环境”，层层组织屏障阻挡免疫细胞浸润，癌细胞还会持续释放抑制信号，让改造后的CAR-T细胞难以识别、杀伤病灶。而Claudin18.2靶点的挖掘，恰好打通了实体瘤CAR-T研发的核心堵点。很多人不了解Claudin18.2，我们可以通俗理解：它是只藏在胃黏膜细胞缝隙里的蛋白，正常组织中免疫细胞根本接触不到；一旦发生胃癌，癌细胞结构破损，这枚专属“肿瘤标识”会大面积暴露在细胞表面。这份高度肿瘤特异性，让它成为CAR-T最理想的攻击靶点，更难得的是，该靶点由中国科研团队耗时十年独立研发验证，无海外成熟研究可参考，属于完全自主的原创突破。参考《胃癌Claudin18.2临床检测专家共识》数据：国内晚期胃及胃食管交界癌患者中，35%-40%存在Claudin18.2阳性表达，是HER2阳性人群（12%-15%）的近三倍，每10名晚期胃癌患者里，就有3-4人有机会从该方案中获益。 99万定价背后：细胞疗法难以压缩的研发与生产成本近百万的定价并非药企随意定价，自体CAR-T全流程高度个性化，成本链条复杂：从患者外周血T细胞采集、体外基因改造、细胞扩增、多轮严苛质控，到回输后全程不良反应监测，每名患者都需要独立定制生产，无法批量标准化制造。放眼全球，海外实体瘤CAR-T同类产品定价普遍超40万美元，国内已上市7款CAR-T产品，定价区间集中在99万-129万元，行业整体成本天花板短期难以突破。高昂定价也暴露行业现实：实体瘤细胞治疗实现了“临床可用”，但距离普通患者“可负担”还有很长距离。想要大幅降价，只能依靠规模化工艺迭代、创新支付体系双管齐下。医保新路径落地：百万CAR-T不再只有自费一条路过去数年，高价CAR-T始终卡在国家医保谈判门槛外，而2025年第八次国谈迎来关键性变革：新增商保创新药专属目录，为高价细胞疗法开辟全新支付渠道。目前国内7款上市CAR-T产品中，5款通过专家评审进入商保议价环节，其中3款同步申报基础医保（详见下表）。我们有理由相信，为了随着未来商业保险、惠民保、药企援助项目结合，会大幅分摊患者自付压力，逐步缩小天价疗法与普通家庭之间的距离。不止胃癌！全癌种CAR-T靶点临床招募汇总除了自费外，当前国内多项CAR-T临床试验同步开展，覆盖血液肿瘤、多类实体瘤。主要针对的癌种和靶点如下： 01 血液肿瘤 ①CD19：用于淋巴瘤、白血病、B细胞急性淋巴细胞白血病等； ②BCMA：用于多发性骨髓瘤等； ③CD20：用于淋巴瘤、B细胞非霍奇金淋巴瘤、弥漫大B细胞淋巴瘤等； ④CD33：用于急性髓细胞白血病等； ⑤CD3：用于多发性骨髓瘤等； ⑥CD7：用于外周T细胞淋巴瘤等； ⑦CD4：用于淋巴瘤等； ⑧CLL-1：用于急性髓细胞白血病等； ⑨EBV：用于淋巴瘤等。 02 实体瘤 ①GPC3：用于肝癌等； ②GUCY2C：用于结直肠癌的治疗； ③PSMA：用于治疗前列腺癌等； ④Claudin18.2：用于胰腺癌、胃癌等； ⑤EGFＲvII：用于治疗神经胶质瘤、头颈部肿瘤等； ⑥MUC-1：用于治疗肺癌、胃癌、胰腺癌、肝癌、结肠癌等； ⑦CEA：用于治疗胰腺癌、肺癌、结肠癌、胃癌、乳腺癌等； ⑧间皮素（mesothelin）：用于治疗间皮瘤、胰腺癌、卵巢癌、肺癌等； ⑨B7-H3：用于治疗尤文肉瘤、髓母细胞瘤、肾母细胞瘤、神经母细胞瘤、横纹肌肉瘤、特别难以治疗的脑干肿瘤（DIPG）等。符合靶点阳性、多线治疗进展的患者，可提交病历至国际干细胞与免疫细胞研究医学部，进行初步评估或了解详细的入排标准。小编寄语十二年前，全球首例CAR-T治愈白血病患儿Emily，让细胞免疫疗法走进大众视野；如今全球超12款CAR-T产品获批，2000余项细胞治疗临床试验同步推进，靶点从单一血液瘤抗原拓展至数十种实体瘤特异性标记，国产技术逐步摆脱海外依赖。从仅延长2.43个月生存期的国产胃癌CAR-T，我们不必陷入“值不值”的单一争论。它真正的意义，是给无药可用的晚期患者多一条选择，也标志国内实体瘤精准免疫治疗正式拉开序幕。医学突破从来不是一步到位彻底攻克癌症，而是不断在绝境里挤出新的生存空间。随着靶点技术迭代、支付体系完善，未来会有更多平价、高效的细胞疗法落地，惠及千万肿瘤家庭。若你或家人确诊胃癌、肺癌、胰腺癌等实体瘤，存在术后复发、靶向耐药、多线治疗进展等情况，想要了解CAR-T、TIL、CAR-NK等前沿免疫疗法，可整理近期病理报告、影像资料、完整治疗记录提交至国际干细胞与免疫细胞研究医学部，免费完成病情适配初评，同步查询各靶点临床试验入组标准。参考资料 [1]Qi C,et al.Claudin18. 2-specific CAR T cells (Satri-cel) versus treatment of physician's choice (TPC) for previously treated advanced gastric or gastroesophageal junction cancer (G/GEJC): Primary results from a randomized, open-label, phase II trial (CT041-ST-01)[J]. 2025. https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4003 本文为“国际干细胞与免疫细胞研究”原创，转载需授权干细胞与免疫细胞研究入群免费领取抗癌细胞资讯｜新技术｜新药研发｜权威专家资料求分享求收藏求点击求在看

100 项与 BCMA(Abzyme Therapeutics) 相关的药物交易

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