A Phase 1, Multicenter, Open-Label Study of CB-010, a CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy, in Patients With Refractory Systemic Lupus Erythematosus (GALLOP)

This is a Phase 1 study to evaluate the safety and efficacy of a single infusion of CB-010 in patients with refractory Systemic Lupus Erythematosus (SLE) with cohorts for lupus nephritis (LN) and extrarenal lupus (ERL).

开始日期2025-03-18

申办/合作机构

Caribou Biosciences, Inc.

NCT04637763

/ Recruiting临床1期

A Phase 1, Multicenter, Open-Label Study of CB-010, a CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy in Patients With Relapsed/Refractory B Cell Non-Hodgkin Lymphoma (ANTLER)

CB010A is a study evaluating safety, emerging efficacy, pharmacokinetics and immunogenicity of CB-010 in adults with relapsed/refractory B cell non-Hodgkin lymphoma after lymphodepletion consisting of cyclophosphamide and fludarabine.

开始日期2021-05-26

申办/合作机构

Caribou Biosciences, Inc.

100 项与 CB-010 相关的临床结果

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100 项与 CB-010 相关的转化医学

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100 项与 CB-010 相关的专利（医药）

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项与 CB-010 相关的文献（医药）

2023-07-01·Cytotherapy

Allogeneic chimeric antigen receptor-T cells with CRISPR-disrupted programmed death-1 checkpoint exhibit enhanced functional fitness.

Article

作者: Fowler, Tristan W. ; Williams, Carolyn ; van Overbeek, Megan ; Lau, Elaine ; Bryan, Mara ; Skoble, Justin ; Kwong, George ; Kohrs, Bryan ; Garner, Elizabeth ; Smith, Stephen C. ; Clarke, Starlynn C. ; Fuller, Chris K. ; McCawley, Shannon ; Sun, Bee-Chun ; Irby, Matthew ; Davis, Ryan T. ; Kanner, Steven B. ; Gradia, Scott ; Donohoue, Paul D. ; Lilley, Graham W. J. ; Storlie, Meghan ; Banh, Lynda ; Edwards, Leslie

BACKGROUND AIMS:

Therapeutic disruption of immune checkpoints has significantly advanced the armamentarium of approaches for treating cancer. The prominent role of the programmed death-1 (PD-1)/programmed death ligand-1 axis for downregulating T cell function offers a tractable strategy for enhancing the disease-modifying impact of CAR-T cell therapy.

METHODS:

To address checkpoint interference, primary human T cells were genome edited with a next-generation CRISPR-based platform (Cas9 chRDNA) by knockout of the PDCD1 gene encoding the PD-1 receptor. Site-specific insertion of a chimeric antigen receptor specific for CD19 into the T cell receptor alpha constant locus was implemented to drive cytotoxic activity.

RESULTS:

These allogeneic CAR-T cells (CB-010) promoted longer survival of mice in a well-established orthotopic tumor xenograft model of a B cell malignancy compared with identically engineered CAR-T cells without a PDCD1 knockout. The persistence kinetics of CB-010 cells in hematologic tissues versus CAR-T cells without PDCD1 disruption were similar, suggesting the robust initial debulking of established tumor xenografts was due to enhanced functional fitness. By single-cell RNA-Seq analyses, CB-010 cells, when compared with identically engineered CAR-T cells without a PDCD1 knockout, exhibited fewer T_reg cells, lower exhaustion phenotypes and reduced dysfunction signatures and had higher activation, glycolytic and oxidative phosphorylation signatures. Further, an enhancement of mitochondrial metabolic fitness was observed, including increased respiratory capacity, a hallmark of less differentiated T cells.

CONCLUSIONS:

Genomic PD-1 checkpoint disruption in the context of allogeneic CAR-T cell therapy may provide a compelling option for treating B lymphoid malignancies.

2023-01-01·Frontiers in network physiology

Assessing cardiorespiratory interactions via lagged joint symbolic dynamics during spontaneous and controlled breathing.

Article

作者: Cairo, Beatrice ; De Maria, Beatrice ; Bari, Vlasta ; Gelpi, Francesca ; Porta, Alberto

Introduction: Joint symbolic analysis (JSA) can be utilized to describe interactions between time series while accounting for time scales and nonlinear features. JSA is based on the computation of the rate of occurrence of joint patterns built after symbolization. Lagged JSA (LJSA) is obtained from the more classical JSA by introducing a delay/lead between patterns built over the two series and combined to form the joint scheme, thus monitoring coordinated patterns at different lags. Methods: In the present study, we applied LJSA for the assessment of cardiorespiratory coupling (CRC) from heart period (HP) variability and respiratory activity (R) in 19 healthy subjects (age: 27-35 years; 8 males, 11 females) during spontaneous breathing (SB) and controlled breathing (CB). The R rate of CB was selected to be indistinguishable from that of SB, namely, 15 breaths·minute^-1 (CB15), or slower than SB, namely, 10 breaths·minute^-1 (CB10), but in both cases, very rapid interactions between heart rate and R were known to be present. The ability of the LJSA approach to follow variations of the coupling strength was tested over a unidirectionally or bidirectionally coupled stochastic process and using surrogate data to test the null hypothesis of uncoupling. Results: We found that: i) the analysis of surrogate data proved that HP and R were significantly coupled in any experimental condition, and coupling was not more likely to occur at a specific time lag; ii) CB10 reduced CRC strength at the fastest time scales while increasing that at intermediate time scales, thus leaving the overall CRC strength unvaried; iii) despite exhibiting similar R rates and respiratory sinus arrhythmia, SB and CB15 induced different cardiorespiratory interactions; iv) no dominant temporal scheme was observed with relevant contributions of HP patterns either leading or lagging R. Discussion: LJSA is a useful methodology to explore HP-R dynamic interactions while accounting for time shifts and scales.

2021-07-16·Organic letters1区 · 化学

Triple Stack of a Viologen Derivative in a CB[10] Pair

1区 · 化学

Article

作者: Bucher, Christophe ; Chowdhury, Shagor ; Gigmes, Didier ; Rosas, Roselyne ; Monnier, Valérie ; Liu, Fengbo ; Bardelang, David ; Karoui, Hakim ; Liu, Simin ; Chevallier, Floris ; Ouari, Olivier ; Kermagoret, Anthony ; Charles, Laurence

A viologen-phenylene-imidazole (VPI) conjugate, previously shown to be singly complexed by CB[7] and doubly bound by CB[8], is herein shown to form antiparallel triple stacks in water with cucurbit[10]uril (CB[10]), pairwise complexing the guest trimer. The quinary host:guest 2:3 complex showed features assignable to charge-transfer interactions. Under reductive conditions, CB[10] could solubilize a VPI radical, even though CB[10] and reduced VPI are almost insoluble, thereby illustrating a possible new application for CB[10].

项与 CB-010 相关的新闻（医药）

2025-01-19

·药明康德

疾病控制率达90%的创新疗法；靶点作用率达95%的PI3Kα共价抑制剂…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. 多肽偶联药物（PDC）AVA6000在治疗唾液腺癌（SGC）患者的1a期临床试验中获得积极数据，疾病控制率（DCR）达90%。 2. 蛋白降解药物BHV-1400在首个人体临床试验中获得积极结果，在最低剂量下只需一次注射，就可在4小时内将致病抗体水平降低60%。 3. PI3Kα共价抑制剂TOS-358在一项1期临床试验中对PI3Kα的靶点作用率达到95%。药明康德内容团队整理 AVA6000：公布1期临床试验数据 Avacta Therapeutics公司宣布，其在研多肽偶联药物AVA6000在治疗唾液腺癌患者的1a期临床试验中获得积极数据。唾液腺癌是一种在转移性阶段尚无标准治疗方案的疾病。AVA6000是Avacta研发管线中的首个多肽偶联药物，由阿霉素（doxorubicin）与Avacta专有的pre|CISION多肽偶联而成，该多肽可在肿瘤微环境中由成纤维细胞激活蛋白-α（FAP）特异性切割。FAP在大多数实体瘤中，与健康组织相比表达水平显著升高。Avacta的多肽偶联药物利用这一特征在肿瘤微环境中特异性释放活性药物，从而降低系统暴露和毒性，为患者提供最佳治疗效果。此次公布的数据显示，AVA6000在唾液腺癌患者中实现了显著且具有临床意义的肿瘤缩小。在接受250 mg/m²及以上剂量治疗的10名唾液腺癌患者中，DCR达90%，5名患者肿瘤显著缩小，其中包括一例部分缓解（PR，肿瘤缩小45%）和四例轻微缓解（MR，肿瘤缩小10%-19.5%）。安全性方面，在每两周一次和每三周一次两个剂量组中，AVA6000的耐受性良好，与常规剂量阿霉素相比，其血液学和心脏毒性明显降低。目前尚未在任一剂量组中确定最大耐受剂量（MTD）。 BHV-1400：公布1期临床试验的初步数据 Biohaven公司公布了其蛋白降解药物管线中的双特异性分子BHV-1400的最新结果。BHV-1400是一款基于耶鲁大学（Yale University）的MoDE技术的双特异性分子，它的一端与半乳糖缺乏型IgA1（Gd-IgA1）抗体结合，另一端与肝细胞表面的去唾液酸糖蛋白受体（ASGPR）结合。ASGPR介导肝细胞通过内吞过程，将靶点蛋白吞入细胞内进行降解。IgA肾病是由于Gd-IgA1的过度生产造成的，BHV-1400通过降低血液循环和肾脏中的Gd-IgA1水平，有望从根源治疗IgA肾病。此次公布的初步数据显示，BHV-1400在首个人体临床试验中获得积极结果，在最低剂量下只需一次注射，就可在4小时内将致病抗体水平降低60%。在某些患者中，观察到在8小时内将Gd-IgA1水平降低70%。此外，Gd-IgA1水平的降低在单次注射后可维持数天。安全性方面，迄今为止，BHV-1400在1期临床试验中的安全性和耐受性良好，未发现具有临床意义的先天和适应性免疫力的变化，并且未观察到剂量限制性毒性。这项研究将继续提高BHV-1400的剂量，探索降低Gd-IgA1水平的范围。基于该研究的积极结果，该公司还计划直接启动关键性临床试验，评估BHV-1400治疗IgA肾病的疗效和安全性。 ▲BHV-1400快速降低Gd-IgA1水平（图片来源：Biohaven公司官网） TOS-358：公布1期临床试验数据 Totus Medicines公司公布了其在研PI3Kα共价抑制剂TOS-358的1期临床试验数据。TOS-358是一款具高度特异性、强效的PI3Kα抑制剂，可在临床前模型中实现近100%的PI3Kα抑制，诱导带有PI3Kα突变的异种移植实体瘤的细胞死亡，包含结直肠癌、肺癌、乳腺癌、卵巢癌、食管癌、头颈癌，且几乎没有观察到非靶向抑制。此次公布的研究结果表明，TOS-358在低至5 mg每日两次（BID）的剂量下具有泛突变临床活性，对PI3Kα的靶点作用率达到95%，且观察到未经确认的完全缓解（CR）。安全性方面，未报道3/4级毒性。值得注意的是，几名接受给药的患者现在已超过6个月未发生进展。在成功完成1期剂量递增研究后，该公司现在启动了一项扩展研究，针对乳腺癌、子宫内膜癌、尿路上皮癌和头颈癌。 ORIC-944：公布1b期联合治疗试验数据 ORIC Pharmaceuticals公司公布了其选择性PRC2别构抑制剂ORIC-944联用阿帕鲁胺治疗转移性去势抵抗性前列腺癌（mCRPC）的1b期临床试验数据。截至2024年12月10日的数据，6例患者中有3例达到确认的PSA50应答（即PSA水平降低50%），其中2例达到确认的PSA90应答。所有PSA应答均维持≥12周，其中包括一例在38周时仍然持续的、确认的PSA90应答。 Soquelitinib：公布1期临床试验的中期数据 Corvus Pharmaceuticals公司公布了其小分子白细胞介素-2诱导的T细胞激酶（ITK）抑制剂soquelitinib用于治疗中度至重度特应性皮炎的1期临床试验的新中期数据。ITK是一种主要表达于T细胞中的酶，在T细胞和自然杀伤（NK）细胞的免疫功能中起重要作用。通过抑制ITK，soquelitinib有望抑制自身免疫和炎症反应。此次公布的结果显示，与安慰剂相比，soquelitinib治疗组在研究者总体评估（IGA）评分为0/1（皮肤症状清除或几乎清除）和湿疹面积和严重度指数较基线减少75%（EASI 75）这些临床终点方面显示出良好的疗效特征。在soquelitinib组的19例患者中，26%的患者达到IGA 0/1，37%的患者达到EASI 75。在安慰剂组的7例患者中，没有人达到IGA 0/1，也没有人达到EASI 75。安全性方面，未观察到明显的安全问题，也未发现临床上显著的实验室检测异常。 ▲治疗第28天达到终点IGA 0/1、EASI 75的患者占比（图片来源：参考资料[4]） ISM5411：公布两项1期临床试验数据英矽智能（Insilico Medicine）公司宣布，其自主研发的候选药物ISM5411已完成在澳大利亚和中国开展的两项1期研究，并取得了积极的初步结果。ISM5411是一种潜在用于治疗炎症性肠病（IBD）的小分子抑制剂，靶向PHD1/2靶点且具有新颖的分子结构，该候选药物设计和优化得到了英矽智能生成化学平台Chemistry42的支持。此次公布的结果显示，在所有剂量组中ISM5411均表现出良好的安全性和耐受性，并初步验证了肠道限制性药代动力学（PK）特征。基于1期临床试验的积极结果，英矽智能预计将于2025年下半年启动一项评估ISM5411在活动性溃疡性结肠炎患者中的2期临床试验。 MBX 1416：公布1期临床试验数据 MBX Biosciences公司公布了在健康成年受试者中开展的MBX 1416单剂量递增和多剂量递增临床试验的积极结果。MBX 1416是一种长效胰高血糖素样肽1（GLP-1）受体拮抗剂，用于治疗减肥后的低血糖症（PBH）。MBX 1416采用MBX公司新颖、专有的精准内分泌肽（PEP）平台设计，旨在防止PBH患者发生严重低血糖，使他们能够过上更健康、更独立的生活。此次公布的结果显示，MBX 1416通常安全性和耐受性良好，并且具有良好的药代动力学特征，支持每周一次给药。基于这些结果，该公司计划于2025年下半年在PBH患者中启动一项2期研究，以进一步优化剂量。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] Avacta Announces Positive New Data from the AVA6000 Phase 1 trial Demonstrating Clinically Meaningful Tumor Shrinkage in Patients with Salivary Gland Cancers. Retrieved January 16, 2025, from https://www.globenewswire.com/news-release/2025/01/16/3010665/0/en/Avacta-Announces-Positive-New-Data-from-the-AVA6000-Phase-1-trial-Demonstrating-Clinically-Meaningful-Tumor-Shrinkage-in-Patients-with-Salivary-Gland-Cancers.html [2] Biohaven Highlights Portfolio Progress, Innovation, and Anticipated Milestones at the 43rd Annual J.P. Morgan Healthcare Conference; Reports Positive Degrader Data with Rapid, Deep, and Selective Lowering of Galactose-Deficient IgA1 with Next Generation Potential Therapy for IgA Nephropathy. Retrieved January 14, 2025, from https://www.prnewswire.com/news-releases/biohaven-highlights-portfolio-progress-innovation-and-anticipated-milestones-at-the-43rd-annual-jp-morgan-healthcare-conference-reports-positive-degrader-data-with-rapid-deep-and-selective-lowering-of-galactose-deficient-ig-302349336.html [3] Totus Medicines Announces Successful Completion of a Phase 1 Dose-Escalation Study and Initiation of an Expansion Trial Evaluating TOS-358, a Covalent PI3Ka Selective Therapy for the Treatment of Select Solid Tumors and Appoints Zelanna Goldberg as Chief Medical Officer. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/10/3007658/0/en/Totus-Medicines-Announces-Successful-Completion-of-a-Phase-1-Dose-Escalation-Study-and-Initiation-of-an-Expansion-Trial-Evaluating-TOS-358-a-Covalent-PI3Ka-Selective-Therapy-for-th.html [4] Corvus Pharmaceuticals Announces Data from Cohort 2 of Placebo-Controlled Phase 1 Clinical Trial of Soquelitinib for Atopic Dermatitis. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008374/0/en/Corvus-Pharmaceuticals-Announces-Data-from-Cohort-2-of-Placebo-Controlled-Phase-1-Clinical-Trial-of-Soquelitinib-for-Atopic-Dermatitis.html [5] ORIC® Pharmaceuticals Provides Early Phase 1b Combination Data for ORIC-944, Operational Highlights for 2024, and Anticipated Upcoming Milestones. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008495/0/en/ORIC-Pharmaceuticals-Provides-Early-Phase-1b-Combination-Data-for-ORIC-944-Operational-Highlights-for-2024-and-Anticipated-Upcoming-Milestones.html [6] 英矽智能公布炎症性肠病药物ISM5411两项I期临床试验的积极结果. Retrieved January 17, 2025, from https://www.prnasia.com/story/474986-1.shtml [7] MBX Biosciences Announces Positive Phase 1 Topline Results for MBX 1416 for the Treatment of Post-bariatric Hypoglycemia. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/07/3005223/0/en/MBX-Biosciences-Announces-Positive-Phase-1-Topline-Results-for-MBX-1416-for-the-Treatment-of-Post-bariatric-Hypoglycemia.html [8] Mersana Therapeutics Announces Positive Initial Clinical Data from Phase 1 Clinical Trial of Emiltatug Ledadotin (XMT-1660); Initiation of Expansion in Triple Negative Breast Cancer. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/10/3007493/0/en/Mersana-Therapeutics-Announces-Positive-Initial-Clinical-Data-from-Phase-1-Clinical-Trial-of-Emiltatug-Ledadotin-XMT-1660-Initiation-of-Expansion-in-Triple-Negative-Breast-Cancer.html [9] Axcynsis Therapeutics Receives FDA Clearance for IND Application of AT03-65, a Differentiated CLDN6-Targeting ADC, Powered by AxcynDOT™ Technology. Retrieved January 17, 2025, from https://www.prnewswire.com/news-releases/axcynsis-therapeutics-receives-fda-clearance-for-ind-application-of-at03-65-a-differentiated-cldn6-targeting-adc-powered-by-axcyndot-technology-302350114.html [10] Ocugen, Inc. Announces Positive 2-Year Data Across Multiple Mutations from Phase 1/2 Clinical Trial of OCU400 —A Novel Modifier Gene Therapy for Retinitis Pigmentosa. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008252/0/en/Ocugen-Inc-Announces-Positive-2-Year-Data-Across-Multiple-Mutations-from-Phase-1-2-Clinical-Trial-of-OCU400-A-Novel-Modifier-Gene-Therapy-for-Retinitis-Pigmentosa.html [11] Verismo Therapeutics Announces First Patient Infused in Phase 1 CELESTIAL-301 Clinical Trial of SynKIR™-310. Retrieved January 17, 2025, from https://www.prnewswire.com/news-releases/verismo-therapeutics-announces-first-patient-infused-in-phase-1-celestial-301-clinical-trial-of-synkir-310-302347464.html [12] Caribou Biosciences Initiates the CB-010 GALLOP Phase 1 Trial in Lupus and Provides Outlook for Multiple Clinical Datasets in 2025. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008079/0/en/Caribou-Biosciences-Initiates-the-CB-010-GALLOP-Phase-1-Trial-in-Lupus-and-Provides-Outlook-for-Multiple-Clinical-Datasets-in-2025.html [13] Arcturus Therapeutics Announces Initiation of Phase 1 H5N1 Flu Vaccine Trial. Retrieved January 17, 2025, from https://ir.arcturusrx.com/news-releases/news-release-details/arcturus-therapeutics-announces-initiation-phase-1-h5n1-flu [14] Korro Bio Announces Dosing of First Participants in REWRITE Phase 1/2a Study of KRRO-110 for Alpha-1 Antitrypsin Deficiency and Provides Pipeline Update. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008445/0/en/Korro-Bio-Announces-Dosing-of-First-Participants-in-REWRITE-Phase-1-2a-Study-of-KRRO-110-for-Alpha-1-Antitrypsin-Deficiency-and-Provides-Pipeline-Update.html [15] NextCure Announces First Patient Dosed in the Phase 1 Study of LNCB74 (B7-H4 ADC) as Therapeutic for Treating Multiple Cancers. Retrieved January 17, 2025, from https://ir.nextcure.com/news-releases/news-release-details/nextcure-announces-first-patient-dosed-phase-1-study-lncb74-b7 [16] LAVA Doses First Patient in Phase 1 LAVA-1266 Study in Hematological Cancers. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/10/3007674/0/en/LAVA-Doses-First-Patient-in-Phase-1-LAVA-1266-Study-in-Hematological-Cancers.html [17] Context Therapeutics Announces First Patient Dosed in the Phase 1 Clinical Trial of CTIM-76. Retrieved January 17, 2025, from https://www.globenewswire.com/de/news-release/2025/01/14/3009673/0/en/Context-Therapeutics-Announces-First-Patient-Dosed-in-the-Phase-1-Clinical-Trial-of-CTIM-76.html [18] Ocugen, Inc. Announces First Patient Dosed in Phase 1 Clinical Trial of OCU200—a Novel Integrin-Targeting Biologic for Diabetic Macular Edema. Retrieved January 17, 2025, from https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-first-patient-dosed-phase-1-clinical-trial [19] ProMIS Neurosciences Initiates Phase 1b Clinical Trial (PRECISE-AD) in Alzheimer’s Disease. Retrieved January 17, 2025, from https://www.promisneurosciences.com/news-media/press-releases/detail/236/promis-neurosciences-initiates-phase-1b-clinical-trial [20] Aptose Announces First AML Patients Dosed with Tuspetinib Triplet Frontline Therapy in TUSCANY Trial. Retrieved January 17, 2025, from https://www.aptose.com/news-media/press-releases/detail/307/aptose-announces-first-aml-patients-dosed-with-tuspetinib [21] ORYZON announces first patient dosed in NCI-sponsored iadademstat in combination with venetoclax and azacitidine clinical trial in first line acute myeloid leukemia. Retrieved January 17, 2025, from https://www.oryzon.com/en/news-events/news/oryzon-announces-first-patient-dosed-nci-sponsored-iadademstat-combination [22] 한미약품-GC녹십자, ‘파브리병’ 국내 1/2상 IND 승인. Retrieved January 17, 2025, from https://www.biospectator.com/news/view/24043 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床结果临床1期多肽偶联药物

2025-01-18

·药明康德

完全缓解率达70%的CAR-T疗法；使100%患者视觉功能改善或稳定达2年的基因疗法…… | CGT周报

▎药明康德内容团队编辑近期，全球细胞和基因疗法（CGT）领域迎来系列进展。用于治疗儿童和成人早期至晚期视网膜色素变性（RP）的基因疗法OCU400更新积极的2年数据，100%可评估患者的视觉功能在一年和两年时均保持稳定或有所改善。用于治疗难治/复发性CD7阳性急性髓系白血病（AML）的新型嵌合抗原受体（CAR）T细胞疗法在一项1期临床试验中取得积极结果，70%的患者在骨髓中实现了完全缓解（CR），60%达到了微小残留病（MRD）阴性CR。本文将节选其中部分重要进展做简单介绍，仅供读者参阅。图片来源：123RF ———✦研发进展✦——— ◇ GenSight Biologics公司公布了单侧眼睛接受其基因疗法Lumevoq（lenadogene nolparvovec）治疗的遗传性视神经病变（LHON）患者的5年随访数据，这些患者都参加了3期RESCUE和REVERSE研究，并在这两项研究结束后接受了长期RESTORE研究。结果显示，在接受Lumevoq一次性治疗5年后，LHON患者表现出双侧视力的持续改善和良好的安全性。66.1%的患者在至少一只眼中实现了从最低点（nadir）起至少3行的最佳矫正视力（BCVA）改善。到5年随访结束时，80.6%的参与者在至少一只眼中达到了可用视力图表测量的视力（BCVA≤1.6 LogMAR）。此外，受试者在多个生活质量评估指标上与基线相比显示出具有临床意义的改善。 ▲在长期随访研究RESTORE中，患者的BCVA相对于最低点的变化（图片来源：参考资料[1]） LHON是一种罕见的遗传性疾病，主要由线粒体基因突变引起，会导致不可逆转的永久性视力丧失。95%的LHON患者携带的基因突变出现在ND1，ND4和ND6基因上，而ND4基因突变是导致大多数LHON病例的原因。Lumevoq是一种利用AAV2载体递送正常人类线粒体ND4基因的基因疗法，而且AAV2载体携带的ND4基因带有特定线粒体靶向序列（MTS），可以促进蛋白在线粒体中的表达。 ◇ Ocugen公司公布了其基因疗法OCU400用于治疗儿童和成人早期至晚期视网膜色素变性的1/2期临床试验的2年新数据。结果显示，与未经治疗的眼睛相比，100%（9/9）接受治疗可评估患者的视觉功能在一年和两年时均保持稳定或有所改善。在两年时，无论患者的突变情况如何，其治疗眼与未治疗眼相比，在视觉功能上的改善均具有统计学意义（P=0.01）。100%（9/9）接受治疗的可评估受试者的活动能力测试均保持稳定或有所改善，这种测试只进行了一年。此外，OCU400治疗的长期安全性和耐受性良好，没有发生与OCU400相关的严重不良事件。 OCU400是一款靶向视网膜核激素受体基因NR2E3的基因疗法。NR2E3基因能够调节视网膜内的多种生理功能，例如感光细胞的发育和维持、新陈代谢、光转导、炎症和细胞生存网络。OCU400通过NR2E3的驱动功能，能够重置被改变的细胞基因网络并建立体内平衡，有望改善遗传性视网膜疾病患者的视网膜健康和功能。 ◇ Caribou Biosciences公司宣布启动其同种异体CAR-T细胞疗法CB-010治疗狼疮肾炎（LN）和肾外狼疮（ERL）的1期临床试验。CB-010利用基因编辑技术生成，除了表达靶向CD19的嵌合抗原受体，还利用基因编辑技术敲除了免疫检查点蛋白PD-1的表达，旨在通过限制CAR-T细胞过早耗竭来提高CAR-T细胞的活性。新闻稿指出，CB-010是临床上首个敲除PD-1的同种异体CAR-T细胞疗法。 ◇ 西比曼生物科技（AbelZeta）宣布，其针对CD20或CD19阳性的复发性或难治性大B细胞淋巴瘤（r/r DLBCL）的CAR-T细胞治疗药物C-CAR039在2期关键确证性临床试验中，成功完成了首例受试者的回输。C-CAR039采用创新的CAR-T细胞工程技术，靶向CD20或CD19抗原，能够精准识别并杀灭肿瘤细胞。相比传统治疗方法，C-CAR039具有更高的特异性和较低的副作用风险，显示出显著的临床优势。 ◇ Blood期刊上近日发表了一项1期研究结果，一种基于纳米抗体的CD7靶向CAR-T细胞疗法用于治疗难治/复发性CD7阳性急性髓系白血病的表现积极。在接受dVHH NS7CAR-T细胞输注后第28天，70%（7/10）的患者在骨髓中实现了CR，其中6人达到了MRD阴性CR。3例无应答（NR）患者均被发现CD7抗原丢失。中位随访时间为178天时，7例CR患者中有3例在接受细胞疗法约2个月后接受了巩固性的第二次同种异体造血干细胞移植，1例患者在随访401天时仍处于缓解状态。安全性方面，大多数患者（80%）出现1-2级细胞因子释放综合征（CRS），没有报告神经毒性。 ◇ 成都优赛诺宣布其自主研发的CD19靶向同种异体通用型CAR-T细胞注射液UC101的IND申请获得了美国FDA的批准。UC101采用独特的基因编辑组合，在降低免疫原性、增加有效性的同时可更好控制不良反应。新闻稿指出，UC101是全球首个获得FDA的IND批准的脐血来源同种异体通用型CAR-T疗法。 ◇ 科济药业宣布其自主研发的一款靶向CD19/CD20的通用型CAR-T细胞治疗候选产品KJ-C2219已完成研究者发起的临床试验（IIT）的首例受试者给药。KJ-C2219基于其THANK-u Plus平台开发，计划用于治疗血液恶性肿瘤和自身免疫性疾病，目前正在中国开展一项针对复发/难治性B细胞非霍奇金淋巴瘤（R/R B-NHL）的IIT试验。 ———✦融资、合作、M&A✦——— 图片来源：123RF ◇ Umoja Biopharma公司宣布完成1亿美元的C轮融资，所得资金将用于推进其体内CAR-T细胞疗法产品线，包括在多项肿瘤学和自身免疫学临床研究中开展的主打项目CD22靶向CAR-T疗法UB-VV400，和CD19靶向CAR-T细胞疗法UB-VV111。Umoja的VivoVec基因递送平台将第三代慢病毒载体基因递送技术与一种新型的T细胞靶向和活化表面复合物相结合，这使得在患者体内得以制造抗癌CAR-T细胞，并潜在消除一些与传统CAR-T方法相关的挑战，包括依赖收集患者自身或供体细胞、相关的细胞生产时间滞后、离体细胞在输送回患者之前需经外部修饰的生产挑战，以及患者在治疗前需要进行淋巴细胞清除。 ◇ Be Biopharma公司宣布完成9200万美元的C轮融资，所得资金将主要用于推进其用于治疗血友病B的主打项目BE-101在1/2期临床试验BeCoMe-9中进行概念验证，并推动其用于治疗低磷酸酶症（HPP）的候选药物BE-102进入临床试验阶段。这两个项目都是基于Be Biopharma的B细胞药物平台建立的，该平台能够创建持久、可调节剂量并且可以重复给药的治疗性产品，这些产品不需要预先处理，并且能够产生持续稳定的治疗性蛋白质水平。 ◇ RhyGaze公司宣布获得了8600万美元的A轮融资，所得资金将用于进一步开发其主要临床候选疗法，这是一种新的基因治疗手段，旨在通过光遗传学技术恢复因疾病导致失明患者的视力。 ◇ REGENXBIO公司与Nippon Shinyaku公司共同宣布建立战略合作伙伴关系，共同开发和商业化治疗II型黏多糖贮积症（MPS II）的基因疗法RGX-121和治疗1型粘多糖贮积症（MPS I）的基因疗法RGX-111。根据协议条款，REGENXBIO将获得1.1亿美元的预付款，并有可能获得高达7亿美元的里程碑付款。Nippon Shinyaku将在美国和亚洲主导首批潜在的MPS II和MPS I基因疗法的商业化进程。REGENXBIO保留了RGX-121优先审评券（PRV）的权利，有望在2025年获得加速批准。该公司正在滚动提交RGX-121的生物制品许可申请（BLA）。 ◇ Orna Therapeutics公司和上海先博生物科技有限公司宣布进一步深化合作伙伴关系，正式将B细胞成熟抗原（BCMA）列为指定的生物靶点，共同推进体内CAR-T疗法的开发与应用。这一合作旨在充分利用双方在环状RNA（oRNA）技术和细胞治疗领域的领先优势，开发创新疗法，为全球患者提供突破性治疗方案。根据协议，先博生物将负责在大中华区内针对BCMA的体内panCAR细胞疗法的研发和商业化工作，而Orna将保留在全球其他地区的研发和商业化全部权益。双方在各自的授权地域内都将有权收到合作首付款以及基于临床开发、上市和商业化等重要阶段的里程碑付款等款项。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] GenSight Biologics Announces Publication of 5-Year Outcomes for Patients Treated Unilaterally with LUMEVOQ® Gene Therapy. Retrieved January 17, 2025, from https://www.gensight-biologics.com/2025/01/15/gensight-biologics-announces-publication-of-5-year-outcomes-for-patients-treated-unilaterally-with-lumevoq-gene-therapy/ [2] Ocugen, Inc. Announces Positive 2-Year Data Across Multiple Mutations from Phase 1/2 Clinical Trial of OCU400 —A Novel Modifier Gene Therapy for Retinitis Pigmentosa. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008252/0/en/Ocugen-Inc-Announces-Positive-2-Year-Data-Across-Multiple-Mutations-from-Phase-1-2-Clinical-Trial-of-OCU400-A-Novel-Modifier-Gene-Therapy-for-Retinitis-Pigmentosa.html [3] Caribou Biosciences Initiates the CB-010 GALLOP Phase 1 Trial in Lupus and Provides Outlook for Multiple Clinical Datasets in 2025. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008079/0/en/Caribou-Biosciences-Initiates-the-CB-010-GALLOP-Phase-1-Trial-in-Lupus-and-Provides-Outlook-for-Multiple-Clinical-Datasets-in-2025.html [4] C-CAR039关键确证性临床试验顺利完成首例受试者回输，迈向新里程碑. Retrieved January 17, 2025, from https://mp.weixin.qq.com/s/WBGOQ8Mq2fqdGAvZyYWPKQ [5] 陆道培医学团队在Blood杂志发表CD7 CAR-T治疗急性髓系白血病最新研究. Retrieved January 17, 2025, from https://www.prnasia.com/story/475830-1.shtml [6] 科济药业通用型CD19/CD20 CAR-T产品完成IIT首例受试者给药. Retrieved January 17, 2025, from https://www.prnasia.com/story/475653-1.shtml [7] 全球首个！成都优赛诺脐血来源异体通用型CAR-T获批美国FDA IND. Retrieved January 17, 2025, from https://mp.weixin.qq.com/s?__biz=MzI0OTUwODU5Mg==&mid=2248128054&idx=2&sn=f31556ef518266a4bd586ce52456bcf1&chksm=e8ccc76ae389d95de29d4959a1286b84ff92147b7655400101a536c4d1b5a27b1a7295b30bdf#rd [8] Umoja Biopharma Announces Oversubscribed $100 Million Series C Financing to Advance In Vivo CAR T Pipeline through Key Oncology Clinical Milestones. Retrieved January 17, 2025, from https://www.umoja-biopharma.com/news/umoja-biopharma-announces-oversubscribed-100-million-series-c-financing-to-advance-in-vivocar-t-pipeline-through-key-oncology-clinical-milestones/ [9] Be Bio Announces Closing of $92M Series C Financing and Completes Transition to a Multi-Program, Clinical Stage Company. Retrieved January 17, 2025, from https://be.bio/be-bio-announces-closing-of-92m-series-c-financing-and-completes-transition-to-a-multi-program-clinical-stage-company/ [10] Institute of Molecular and Clinical Ophthalmology Basel Spinout RhyGaze Closes USD 86 Million Series A Round to Further Novel Gene Therapy for Vision Restoration. Retrieved January 17, 2025, from https://www.businesswire.com/news/home/20250110360650/en/Institute-of-Molecular-and-Clinical-Ophthalmology-Basel-Spinout-RhyGaze-Closes-USD-86-Million-Series-A-Round-to-Further-Novel-Gene-Therapy-for-Vision-Restoration [11] REGENXBIO and Nippon Shinyaku Announce Exclusive Partnership to Develop and Commercialize RGX-121 and RGX-111 for MPS Diseases. Retrieved January 17, 2025, from https://www.prnewswire.com/news-releases/regenxbio-and-nippon-shinyaku-announce-exclusive-partnership-to-develop-and-commercialize-rgx-121-and-rgx-111-for-mps-diseases-302350270.html [12] Orna Therapeutics与Simnova扩展合作，聚焦BCMA体内CAR-T疗法的开发. Retrieved January 17, 2025, from https://mp.weixin.qq.com/s/c4xvuPDkNlTmb9xsZ_WpJw 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

基因疗法细胞疗法临床结果免疫疗法临床3期

2024-12-30

·PRNewswire

Stockholder Notice: Robbins LLP Informs Stockholders of Caribou Biosciences, Inc. of the Class Action Lawsuit

SAN DIEGO, Dec. 30, 2024 /PRNewswire/ -- Robbins LLP informs investors that a class action was filed on behalf of all persons and entities that purchased or otherwise acquired Caribou Biosciences, Inc. (NASDAQ: CRBU) securities between July 14, 2023 and July 16, 2024. Caribou is a clinical-stage biopharmaceutical company that purports to develop genome-edited allogeneic cell therapies for the treatment of hematologic malignancies in the U.S. and internationally. For more information, submit a form, email attorney Aaron Dumas, Jr., or give us a call at (800) 350-6003. The Allegations: Robbins LLP is Investigating Allegations that Caribou Biosciences, Inc. (CRBU) Misled Investors Regarding the Efficacy of its Lead Drug Candidate According to the complaint, during the class period, defendants failed to disclose that: that: (i) they had overstated CB-010's safety, efficacy, and durability relative to approved autologous CAR-T cell therapies in treating patients with r/r B-NHL and/or LBCL, as well as CB-010's overall clinical results and commercial prospects; (ii) Caribou was at significant risk of having insufficient cash, liquidity, and/or other capital to fund its current business operations, including preclinical research activities associated with the allogeneic CAR-NK platform; and (iii) all the foregoing was likely to have a significant negative impact on Caribou's business and operations. The complaint alleges that on June 2, 2024, Caribou issued a press release announcing that it had "presented updated clinical data from the ongoing ANTLER Phase 1 trial that [purportedly] indicates a single dose of CB-010 . . . has the potential to rival the safety, efficacy, and durability of approved autologous CAR-T cell therapies." In response, Evercore ISI analysts downgraded Caribou stock to "in line" and dropped their price target to $3.00 from $13. On this news, Caribou's stock price fell 25.52%, to close at $2.145 per share on June 3, 2024. The complaint further alleges that on July 16, 2024, Caribou disclosed in an SEC filing that it had "discontinued preclinical research activities associated with its allogeneic CAR-NK platform and reduced its workforce by 21 positions, or approximately 12%", explaining that "[t]he Company is undertaking this reduction to extend its cash runway". On this news, Caribou's stock price fell 3.3%, to close at $2.64 per share on July 17, 2024. What Now: You may be eligible to participate in the class action against Caribou Biosciences, Inc. Shareholders who want to serve as lead plaintiff for the class must submit their application to the court by February 24, 2025. A lead plaintiff is a representative party who acts on behalf of other class members in directing the litigation. You do not have to participate in the case to be eligible for a recovery. If you choose to take no action, you can remain an absent class member. For more information, click here. All representation is on a contingency fee basis. Shareholders pay no fees or expenses. About Robbins LLP: A recognized leader in shareholder rights litigation, the attorneys and staff of Robbins LLP have been dedicated to helping shareholders recover losses, improve corporate governance structures, and hold company executives accountable for their wrongdoing since 2002. To be notified if a class action against Caribou Biosciences, Inc. settles or to receive free alerts when corporate executives engage in wrongdoing, sign up for Stock Watch today. Attorney Advertising. Past results do not guarantee a similar outcome. SOURCE Robbins LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床1期细胞疗法免疫疗法临床结果

100 项与 CB-010 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
难治性B细胞淋巴瘤	临床1期	美国	Caribou Biosciences, Inc.	2021-05-26
难治性B细胞淋巴瘤	临床1期	澳大利亚	Caribou Biosciences, Inc.	2021-05-26
难治性B细胞淋巴瘤	临床1期	以色列	Caribou Biosciences, Inc.	2021-05-26
复发性非霍奇金淋巴瘤	临床1期	美国	Caribou Biosciences, Inc.	2021-05-26
复发性非霍奇金淋巴瘤	临床1期	澳大利亚	Caribou Biosciences, Inc.	2021-05-26
复发性非霍奇金淋巴瘤	临床1期	以色列	Caribou Biosciences, Inc.	2021-05-26
肾外狼疮	临床1期	美国	Caribou Biosciences, Inc.	-

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适应症

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04637763 (ANTLER, ASCO2024) 人工标引	临床1期	B细胞淋巴瘤	16	CB-010 at 40 x 106 CAR-T cells	糧願艱糧遞網鏇製獵夢(鹹積鹽蓋簾網蓋艱積餘) = Not seen. 積蓋蓋齋網鏇繭顧襯齋 (網觸願鹽願夢築鬱鑰鹽 ) 更多	积极	2024-05-24
				CB-010 at 80 x 106 CAR-T cells
NCT04637763 (ANTLER, EHA 12024 \| EHA 22024) 人工标引	临床1期	非霍奇金淋巴瘤	16	CB-010	鹹醖膚窪鹹構膚襯選蓋(築淵憲網鏇鑰製選網製) = 願襯襯齋夢鹽醖鹹獵夢繭鏇衊鏇鹽遞構醖糧積 (鹹鏇壓襯顧夢憲窪選鏇 ) 更多	积极	2024-05-14
				CB-010 (LBCL)	鹹醖膚窪鹹構膚襯選蓋(築淵憲網鏇鑰製選網製) = 網衊遞夢獵蓋網襯願簾繭鏇衊鏇鹽遞構醖糧積 (鹹鏇壓襯顧夢憲窪選鏇 ) 更多
NCT04637763 (ANTLER, Corporate Publications) 人工标引	临床1期	难治性B细胞淋巴瘤	6	CB-010	夢艱夢築夢獵製廠夢繭(繭窪醖壓網鹹獵夢遞鹽) = 40x10^6 CAR-T cells（grade 1 CRS 33% and grade 3 ICANS 17%）餘積膚構廠製願壓夢遞 (餘築蓋繭願願範積淵襯 )	积极	2022-06-10