Hepatic Artery Transfusion of NKG2D CAR-T Cells to Treat Patients with Previously Treated Liver Metastatic Colorectal Cancer: a Prospective, Multicenter Clinical Trial

开始日期2021-09-01

申办/合作机构

The Third Affiliated Hospital of Guangzhou Medical University Stomatology

ChiCTR2000038015 / Recruiting早期临床1期IIT

One-Center, Open-Label, Single-Arm Clinical Study of the Safety and Effectiveness of NKG2D CAR-T Cells Infusion in the Treatment of Relapsed or Refractory NKG2DL+ Tumors

开始日期2020-09-10

申办/合作机构-

NCT03612739 / Withdrawn临床1期

An Open-label, Phase I Study to Assess the Safety of NKR-2 Treatment Administered Concurrently With 5-azacytidine in Treatment-naïve Acute Myeloid Leukemia or Myelodysplastic Syndrome Patients Not Candidates for Intensive Therapy

This open-label Phase I study aims to define the recommended dose for further clinical development the NKR-2 treatment administered concurrently with AZA in treatment-naïve AML/MDS patients not candidates for intensive chemotherapy or hematopoietic stem cell transplantation.
This Phase I study is divided into three sequential cohorts evaluating three different dose-levels of NKR-2 (1x108, 3x108 and 1x109 NKR-2 per injection) using a 3+3 design evaluate. Further patients will be enrolled at the RecD to reach 9 evaluable patients in total at the RecD.
The study consists of a screening phase, a treatment administration phase and a follow-up phase divided into treatment follow-up (TFU) and long-term safety follow-up (LTSFU). For each patient who received at least one NKR-2 administration, the overall study duration will be 15 years after first NKR-2 administration.

开始日期2018-12-01

申办/合作机构

Celyad Oncology SA

100 项与 CYAD-01(Dartmouth College) 相关的临床结果

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100 项与 CYAD-01(Dartmouth College) 相关的转化医学

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100 项与 CYAD-01(Dartmouth College) 相关的专利（医药）

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项与 CYAD-01(Dartmouth College) 相关的文献（医药）

2023-10-20·Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Co-expression of IL-4/IL-15-based inverted cytokine receptor in CAR-T cells overcomes IL-4 signaling in immunosuppressive pancreatic tumor microenvironment.

Article

作者: Ying Zhou ; Muhammad Asad Farooq ; Iqra Ajmal ; Cong He ; Yaoxin Gao ; Dandan Guo ; Yixin Duan ; Wenzheng Jiang

The efficacy of CAR-T cell therapy has been hindered by several factors that are intrinsic to the tumor microenvironment. Many strategies are being employed to overcome these barriers and improve immunotherapies efficacy. Interleukin (IL)- 4 is a cytokine released by tumor cells inside the tumor microenvironment and it can oppose T cell effector functions via engagement with the IL-4 receptor on the surface of T cells. To overcome IL-4-mediated immunosuppressive signals, we designed a novel inverted cytokine receptor (ICR). Our novel CAR construct (4/15NKG2D-CAR), consisted of an NKG2D-based chimeric antigen receptor, co-expressing IL-4R as an extracellular domain and IL-15R as a transmembrane and intracellular domain. In this way, IL-4R inhibitory signals were converted into IL-15R activation signals downstream. This strategy increased the efficacy of NKG2D-CAR-T cells in the pancreatic tumor microenvironment in vitro and in vivo. 4/15NKG2D-CAR-T cells exhibited increased activation, degranulation, cytokine release, and cytotoxic ability of NKG2D-CAR-T cells against IL-4⁺ pancreatic cell lines. Furthermore, 4/15NKG2D-CAR-T cells exhibited more expansion, less exhaustion, and an increased percentage of less differentiated T cell phenotypes in vitro when compared with NKG2D-CAR-T cells. That is why IL-4R/IL-15R-modified CAR-T cells eradicated more tumors in vivo and outperformed NKG2D-CAR-T cells. Thus, we report here a novel NKG2D-CAR-T cells that could overcome IL-4-mediated immunosuppression in solid tumors.

2023-10-01·Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

Annihilation of Non-small Cell Lung Cancer by NKG2D CAR-T Cells Produced from T Cells from Peripheral Blood of Healthy Donors.

Article

作者: Jinhong Jiang ; Yonghua Liu ; Yuxiao Zeng ; Bingmu Fang ; Yongping Chen

Some progress has been made in immunotherapy with chimeric antigen receptor (CAR)-T cells targeting NKG2D-NKG2DL with the purpose of eradicating solid tumors. Non-small cell lung cancer (NSCLC) has been shown to express NKG2DL. This study hence evaluated the therapeutic effect of NKG2D CAR-T cells on NSCLC. Accordingly, NKG2D CAR-T cells were obtained from diverse human autologous T cell sources. T cells from peripheral blood T lymphocytes of healthy volunteers (without NKG2D CAR insertion) were used as NT-T cells. Coculture of effector cells (CAR-T cells or NT-T cells) with target cells (NSCLC cells such as PC-9 or NCL-H460 cells) was performed at different ratios. The cytotoxicity of CAR-T cells was examined using lactate dehydrogenase assay kits. Murine xenograft assay was conducted to investigate the in vivo antitumor effect of CAR-T cells. Cytokines secreted from CAR-T cells were assessed by enzyme-linked immunosorbent assay. CAR-T cell infiltration into xenografts was observed through immunochemical assay. Based on the results, NKG2DL was highly expressed in NSCLC cells. Compared with NT-T cells, NKG2D CAR-T cells from different sources of T cells delivered stronger toxicity, and secreted more effector and memory function-related cytokines to NSCLC cells, and those from the peripheral blood of healthy donors (H-T cells) exhibited the strongest effect. Furthermore, compared with NT-T cells, H-T cells and NKG2D CAR-T cells from NSCLC patients' peripheral blood diminished tumor, improved survival, increased body weight and tumor-infiltrating capacity, and upregulated serum IFN-γ level in NOG mice. Collectively speaking, NKG2D CAR-T cells exhibit a robust effect on eradicating NSCLC in a NKG2DL-dependent manner, thus making themselves a promising therapeutic candidate for NSCLC patients.

2023-10-01·Heliyon

Lenalidomide improves NKG2D-based CAR-T cell activity against colorectal cancer cells invitro.

Article

作者: Mahdi Zarei ; Shahriyar Abdoli ; Touraj Farazmandfar ; Majid Shahbazi

Introduction:

Although CAR-based immunotherapy is viewed as a promising treatment for tumors, particularly hematological malignancies, solid tumors can pose challenges. It has been suggested that the immunomodulatory medication Lenalidomide (LEN) may increase the effectiveness of CAR T cells in the treatment of solid tumors. The purpose of our study was to investigate the effect of NKG2D-based CAR T cell therapy on colorectal cancer cell lines, and then we assessed combinatorial therapy using NKG2D CAR T cells and lenalidomide in vitro.

Methods and results:

To prepare NKG2D CAR T cells, a second-generation NKG2D-CAR construct was designed and transfected into the T cells using a lentiviral system. The NKG2D CAR T cells showed significantly higher cytotoxic activity against colorectal cancer cell lines, HCT116 and SW480, compared to untransduced T cells. In addition, our data demonstrated that the cytotoxicity and cytokine secretion of NKG2D CAR T cells significantly increased in the presence of higher doses of lenalidomide.

Conclusions:

The study findings suggest that combinational therapy, utilizing NKG2D-based CAR T cells and lenalidomide, has a high potential for effectively eliminating tumor cells in vitro.

项与 CYAD-01(Dartmouth College) 相关的新闻（医药）

2023-02-12

·药明康德

客观缓解率达100%的CAR-T疗法、显著降低脑卒中患者死亡率的神经保护剂… | 一周盘点

▎药明康德内容团队编辑本期看点1. 医院制造的CAR-T细胞疗法GLPG5201用于治疗慢性淋巴细胞白血病和小淋巴细胞淋巴瘤，早期临床结果亮眼，客观缓解率达100%，完全缓解率达86%。2. 靶向BCMA的自体CAR-T细胞疗法NXC-201用于治疗多发性骨髓瘤，2期推荐剂量下的总缓解率达90%。3. 以高特异性作用于TLR4的神经保护剂ApTOLL联合血管内治疗，显著降低缺血性脑卒中患者的死亡率。4. 靶向NKG2D配体的候选CAR-T细胞疗法的概念验证试验结果积极，支持此类疗法的进一步开发。药明康德内容团队整理GLPG5201：公布1/2期临床试验数据Galapagos公司公布了其可在护理点制造的CAR-T细胞疗法GLPG5201的1/2期临床试验结果。靶向CD19的CAR-T治疗具潜力提高患有多种B细胞恶性肿瘤患者的生存率，例如慢性淋巴细胞白血病（CLL）和小淋巴细胞淋巴瘤（SLL）。该公司正在评估医院制造的GLPG5201在复发/难治性（RR）CLL和SLL患者中的可行性、安全性和有效性，这些患者伴或不伴Richter转化（RT）。研究结果显示，医院制造的GLPG5201是可行的，该在研CAR-T细胞疗法能在体内持续且良好地扩增。截至2023年1月9日，7例被诊断为RR-CLL的患者（4例伴RT）的客观缓解率（ORR）达到100%，其中86%（6/7）的患者达到完全缓解（CR），所有伴RT的患者均获得了CR。报告的持续缓解时间已达7.9个月，后续的随访还在进行中。仅有1例患者在达到PR后复发，复发的肿瘤为CD19阴性，且该患者被确诊为RT。安全性方面，GLPG5201表现出可接受的安全性，未观察到免疫效应细胞相关神经毒性综合征（ICANS），观察到的细胞因子释放综合征（CRS）不超过2级。NXC-201：公布1期临床试验的新数据Nexcella公司公布了其靶向BCMA的自体CAR-T细胞疗法NXC-201的1期试验最新数据。该研究旨在评估NXC-201用于治疗复发/难治性多发性骨髓瘤（RRMM）的安全性和有效性。截至2022年10月23日的数据，NXC-201在RRMM患者中表现出潜在有意义的疗效和持久的反应。中位随访时间为146天时，在包含所有剂量组中42位可评估的RRMM患者的总缓解率（ORR）为83%，完全缓解（CR）率或严格意义的完全缓解（sCR）率为50%。在接受2期临床推荐剂量（RP2D）NXC-201的MM患者中，根据国际骨髓瘤工作组的标准，ORR达90%，59%（17/29）的患者达到CR或sCR。此外，NXC-201的耐受性良好，42例可评估的患者中未观察到ICANS，所见CRS为可控。此次公布的数据支持NXC-201作为潜在可在门诊使用的CAR-T细胞疗法。ApTOLL：公布1b/2a期临床试验数据aptaTargets公司公布了其Toll样受体4（TLR4）拮抗剂ApTOLL联合血管内治疗（EVT）用于治疗急性缺血性卒中患者的早期临床结果。卒中可能由流向大脑的血流量显著减少或脑血管破裂出血引起，其中最常见的类型为缺血性卒中（约占85%）。ApTOLL是一种潜在“first-in-class”的神经保护剂，能够以高特异性作用于TLR4，阻断缺血性卒中后发生的炎症反应。此次公布的是一项多中心、双盲、随机、安慰剂为对照的试验，共纳入151例患者。患者被随机分配接受两种剂量的ApTOLL或安慰剂。所有患者都接受了机械血栓切除术，伴或不伴溶栓剂。研究结果显示，与安慰剂组相比，高剂量ApTOLL组的死亡率从18%降低至5%，高剂量ApTOLL组在最终梗死体积的减少和美国国立卫生研究院72小时卒中量表（NIHSS）评分方面的改善均具有统计学意义。研究人员指出，ApTOLL未显示出与缺血性中风药物产生相互作用，这意味着它可以用于大多数患者。此外，ApTOLL的安全性与耐受性均良好。CYAD-01：公布1期临床试验的初步数据Celyad Oncology公司公布了其在研CAR-T细胞疗法CYAD-01在多种血液系统恶性肿瘤中的早期数据。CYAD-01是一款基于自然杀伤受体NKG2D的自体CAR-T疗法。这是一项开放标签的1期剂量递增试验，针对至少接受过一线治疗的复发/难治性急性髓系白血病（AML）、骨髓增生异常综合征（MDS）和多发性骨髓瘤患者开展。与大多数在研CAR-T细胞疗法的研究不同，该研究在没有任何预处理化疗的情况下，对多次单独输注CYAD-01的治疗方案进行了评估。研究结果显示，CYAD-01的安全性良好，12例可评估的AML/MDS患者中有3例达成客观缓解。值得一提的是，该试验患者的中位年龄较大，一般状况较差。在这些难以治疗的患者群体中的数据为靶向NKG2D配体的候选CAR-T细胞疗法提供概念验证，并支持此类疗法的进一步开发。CELZ-201：启动1/2期临床试验CELZ-201是Creative Medical Technology公司开发的一款细胞疗法，目前正在接受评估，作为新诊断的1型糖尿病（T1D）患者的治疗方法。CELZ-201是一种围产期组织衍生细胞（PRDC）疗法，具有PRDC的可自我更新、低抗原性和低毒性的特点，并能在临床上进行大规模扩增。STAR-0215：启动1b/2期临床试验STAR-0215是Astria Therapeutics公司开发的血浆激肽释放酶单克隆抗体抑制剂，旨在为遗传性血管性水肿（HAE）患者提供长效且有效的预防性治疗选择，设计以每3个月或更长周期给药一次。此前，该公司已公布了STAR-0215在健康受试者中的1a期临床试验的初步数据。结果显示，STAR-0215具有作为长效血浆激肽释放酶抑制剂的潜力，预估半衰期长达110天，支持STAR-0215每三个月给药一次或以更低的频率给药。该公司于近日宣布启动在HAE患者中开展的1b/2期试验。HP518：IND申请获得FDA许可HP518是Hinova Pharmaceuticals公司开发的嵌合降解剂，通过靶向雄激素受体（AR）蛋白以治疗转移性去势抵抗性前列腺癌（mCRPC）。AR是一种经验证的前列腺癌治疗靶点，但AR基因的扩增、突变等多种机制会导致癌细胞对药物不产生应答。HP518通过靶向降解AR蛋白，有望克服由某些特定AR基因突变引起的前列腺癌耐药性。在临床前研究中，HP518对野生型AR和一些对恩杂鲁胺耐药的特定AR突变表现出优异的选择性和降解活性。此外，HP518在异种移植小鼠模型中也展现了出色的抗肿瘤作用。AC0676：IND申请获得FDA许可AC0676是由Accutar Biotechnology通过人工智能（AI）赋能药物发现的口服嵌合降解剂分子，旨在靶向并降解布鲁顿酪氨酸激酶（BTK），有潜力用于治疗复发/难治性B细胞恶性肿瘤。BTK在许多B细胞恶性肿瘤的病理生理学中具有关键作用。与基于共价和非共价作用的BTK抑制剂不同，AC0676能够通过同时去除BTK的激酶和支架作用，为B细胞恶性肿瘤患者提供潜在的新治疗选择。在临床前研究中，AC0676能够选择性地有效降解BTK蛋白，覆盖范围广泛，包括BTK野生型和突变体（包括C481S，L528W等）。此外，AC0676具有良好的药理学特性，在动物模型中也展现出潜在的抗肿瘤活性。ART0380：启动2期临床试验ART0380是Artios Pharma公司针对DNA损伤反应（DDR）所开发的新型小分子抑制剂。此药物靶向ATR——一种DNA复制应激反应的主要调节因子，因此可与导致DNA损伤的药物结合使用，以治疗DNA修复缺陷的癌症。目前，ART0380正在被开发与吉西他滨联用，治疗铂耐药的卵巢癌。1期剂量递增试中，ART0380在晚期实体肿瘤中表现出良好的安全性、耐受性、临床活性和药代动力学特征。该公司在近期已启动了在实体肿瘤中首个2期试验的扩展队列研究，针对铂耐药卵巢癌患者的初步数据预计将在2025年上半年公布。Ziftomenib：启动2期临床试验Ziftomenib是Kura Oncology公司开发的新型口服menin抑制剂，靶向menin-KMT2A/MLL蛋白相互作用，用于治疗NPM1突变型AML。此前，ziftomenib已获得美国FDA授予的孤儿药资格，用于治疗AML。Kura公布的1期临床试验结果显示，截至2022年10月24日的数据，接受600 mg剂量ziftomenib的20例NPM1突变型AML患者中有30%达到了CR。此外，该剂量下ziftomenib的安全性和耐受性良好，被指定为RP2D。该候选疗法的2期试验在近期已完成了首批患者给药。Lucid-MS：获加拿大卫生部批准开展1期试验Lucid-MS是FSD Pharma公司开发的一款潜在“first-in-class”、具神经保护性的化合物，并具创新的治疗机制，用于治疗多发性硬化（MS）。MS是由于免疫系统攻击保护神经的髓鞘而产生的慢性自身免疫性疾病。MS的进展导致身体机能（例如步行）和认知功能（例如记忆）的下降。临床前试验显示，Lucid-MS能够避免髓鞘降解（即脱髓鞘反应），这是造成MS与其他神经退化性疾病的原因。此外，还观察到Lucid-MS能够促进MS实验动物模型的功能性恢复。大家都在看药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲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] Accutar Biotechnology Announces FDA Clearance of IND Application for Phase 1 Trial of AC0676 in B-cell Malignancies. Retrieved February 7, 2023, from https://www.businesswire.com/news/home/20230203005452/en[2] Seelos Therapeutics Doses First Patients in an Ethnobridging Study with SLS-002 (Intranasal Racemic Ketamine). Retrieved February 7, 2023, from https://seelos.irpass.com/profiles/investor/NewsPrint.asp?v=6&b=2376&ID=115640&m=rl&g=1201[3] Hinova Receives FDA Proceed Authorization for its IND Application for HP518, an Orally Bioavailable Chimeric Degrader Targeting Androgen Receptor for Prostate Cancer Treatment. Retrieved February 9, 2023, from https://www.prnewswire.com/news-releases/hinova-receives-fda-proceed-authorization-for-its-ind-application-for-hp518-an-orally-bioavailable-chimeric-degrader-targeting-androgen-receptor-for-prostate-cancer-treatment-301739031.html[4] FSD Pharma Receives Regulatory Clearance for Its Proposed Phase-1 Clinical Trial of Lucid-21-302 (Lucid-MS), First-in-Class Multiple Sclerosis Drug Candidate. Retrieved February 10, 2023, from https://www.businesswire.com/news/home/20230207005742/en/[5] Astria Therapeutics Initiates ALPHA-STAR Phase 1b/2 Clinical Trial of STAR-0215 in People with HAE. Retrieved February 10, 2023, from https://www.businesswire.com/news/home/20230208005071/en/[6] Century Therapeutics Announces First Patient Dosed in First-In-Human Phase 1 ELiPSE-1 Trial Evaluating CNTY-101 in Relapsed or Refractory CD19 Positive B-cell Lymphomas. Retrieved February 10, 2023, from https://investors.centurytx.com/news-releases/news-release-details/century-therapeutics-announces-first-patient-dosed-first-human[7] Creative Medical Technology Holdings Announces IRB Approval for FDA Cleared Phase 1/2 Clinical Trial of Novel Cell Therapy for the Treatment of Type 1 Diabetes. Retrieved February 10, 2023, from https://www.prnewswire.com/news-releases/creative-medical-technology-holdings-announces-irb-approval-for-fda-cleared-phase-12-clinical-trial-of-novel-cell-therapy-for-the-treatment-of-type-1-diabetes-301741094.html[8] Seres Therapeutics Announces Initiation of Enrollment in SER-155 Phase 1b Study Cohort 2 in Individuals Undergoing Allogeneic Hematopoietic Stem Cell Transplantation. Retrieved February 10, 2023, from https://www.businesswire.com/news/home/20230208005144/en/[9] Celyad Oncology announces the publication of data from its Phase 1 THINK study of CYAD-01. Retrieved February 10, 2023, from https://www.globenewswire.com/news-release/2023/02/09/2604573/0/en/Celyad-Oncology-announces-the-publication-of-data-from-its-Phase-1-THINK-study-of-CYAD-01.html[10] Immix Biopharma Subsidiary Nexcella, Inc. Presents 42-Patient Interim Data, with 90% Overall Response Rate in Relapsed or Refractory Multiple Myeloma at NXC-201 Therapeutic Dose from its Phase 1 Expansion Trial at the 5th European CAR T-cell Meeting. Retrieved February 10, 2023, from https://www.globenewswire.com/news-release/2023/02/09/2604948/0/en/Immix-Biopharma-Subsidiary-Nexcella-Inc-Presents-42-Patient-Interim-Data-with-90-Overall-Response-Rate-in-Relapsed-or-Refractory-Multiple-Myeloma-at-NXC-201-Therapeutic-Dose-from-i.html[11] KURA ONCOLOGY ANNOUNCES FIRST PATIENTS DOSED IN PHASE 2 REGISTRATION-DIRECTED TRIAL OF ZIFTOMENIB IN NPM1-MUTANT ACUTE MYELOID LEUKEMIA. Retrieved February 10, 2023, from https://ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-announces-first-patients-dosed-phase-2[12] aptaTargets’ ApTOLL reduces mortality from 18% to 5% in a Phase 1b/2a trial in ischemic stroke patients. Retrieved February 10, 2023, from https://aptatargets.com/newsroom/aptoll-reduces-mortality-from-18-to-5-in-a-phase-1b-2a-trial-in-ischemic-stroke-patients/[13] Artios Announces Initiation of Phase 2 Randomized Trial for ATR Inhibitor ART0380 plus Gemcitabine in Patients with Platinum Resistant Ovarian Cancer. Retrieved February 10, 2023, from https://www.artios.com/press-release/artios-announces-initiation-of-phase-2-randomized-trial-for-atr-inhibitor-art0380-plus-gemcitabine-in-patients-with-platinum-resistant-ovarian-cancer/[14] Galapagos presented encouraging initial safety and efficacy data at 2023 EBMT-EHA for point-of-care manufactured CAR-T candidate, GLPG5201, in rrCLL. Retrieved February 10, 2023, from https://ml-eu.globenewswire.com/Resource/Download/94396325-2b75-4b81-8100-32aa817771a9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

细胞疗法免疫疗法临床2期临床结果临床1期

2023-02-09

·GlobeNewswire-Health Care

Celyad Oncology announces the publication of data from its Phase 1 THINK study of CYAD-01

MONT-SAINT-GUIBERT, Belgium, Feb. 09, 2023 (GLOBE NEWSWIRE) -- Celyad Oncology (Euronext & Nasdaq: CYAD) (the “Company”), a biotechnology company focused on the discovery and development of innovative technologies for chimeric antigen receptor (CAR) T-cell therapies, today announces the publication of the data from the haematological arm of the THINK study which evaluated CYAD-01 in relapsed or refractory (r/r) acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) or multiple myeloma (MM) patients. The findings were published in the journal The Lancet Haematology. CYAD-01 is the Company’s first autologous CAR T-cell candidate, based on the natural killer receptor NKG2D, assessed clinically. The completed THINK study was an open-label, dose-escalation Phase 1 study for patients with r/r AML, MDS, or MM, after at least one previous line of therapy. Patients were recruited from five hospitals in the USA and Belgium. The Lancet Haematology publication includes data from the 16 patients treated with CYAD-01 in the dose escalation segment of the study, which evaluated three dose levels of CYAD-01 using a schedule of three infusions at two-week intervals in the absence of any preconditioning chemotherapy. Overall, CYAD-01 showed favourable safety data with signs of clinical activity with three of the 12 evaluable AML/MDS patients presenting an objective response. Importantly, the THINK study is one of the first completed dose-escalation CAR T-cell studies in r/r AML/MDS. Unlike the majority of the studies evaluating CAR T-cell therapy candidates, the THINK study evaluated multiple infusions of CYAD-01 as a stand-alone product candidate (i.e., without prior bridging or preconditioning chemotherapy). This feature is of particular interest considering the median older age and the poorer general condition of patients with r/r AML or MDS at diagnosis. Although the need to improve the anti-tumour activity is warranted, these data in a difficult-to-treat patient population potentially provide the proof-of-concept of targeting NKG2D ligands by a CAR T-cell product candidate, and support the further development of NKG2D-based CAR T-cell therapies. About Celyad Oncology Celyad Oncology is a biotechnology company focused on the discovery and development of innovative technologies for chimeric antigen receptor (CAR) T-cell therapies. The Company is focusing on opportunities to fully harness the true potential of its proprietary technology platforms and intellectual property and support the development of next-generation CAR T candidates in solid tumors and hematological malignancies. Celyad Oncology is based in Mont-Saint-Guibert, Belgium and New York, NY. For more information, please visit www.celyad.com. Celyad Oncology Forward-Looking Statement This release may contain forward-looking statements, within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the potential safety, activity, and feasibility of CYAD-01 cell therapy and other product NKG2D-based candidates or the clinical and commercial potential of these product candidates. The words “potential,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this release are based on management’s current expectations and beliefs and are subject to a number of known and unknown risks, uncertainties and important factors which might cause actual events, results, financial condition, performance or achievements of Celyad Oncology to differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks related to the material uncertainty about the Company’s ability to continue as a going concern; the Company’s ability to realize the expected benefits of its updated strategic business model; the Company’s ability to develop its IP assets and enter into partnerships with outside parties; the Company’s ability to enforce its patents and other IP rights; the possibility that the Company may infringe on the patents or IP rights of others and be required to defend against patent or other IP rights suits; the possibility that the Company may not successfully defend itself against claims of patent infringement or other IP rights suits, which could result in substantial claims for damages against the Company; the possibility that the Company may become involved in lawsuits to protect or enforce its patents, which could be expensive, time-consuming, and unsuccessful; the Company’s ability to protect its IP rights throughout the world; the potential for patents held by the Company to be found invalid or unenforceable; and other risks identified in Celyad Oncology’s U.S. Securities and Exchange Commission (SEC) filings and reports, including in the latest Annual Report on Form 20-F filed with the SEC and subsequent filings and reports by Celyad Oncology. These forward-looking statements speak only as of the date of publication of this document and Celyad Oncology’s actual results may differ materially from those expressed or implied by these forward-looking statements. Celyad Oncology expressly disclaims any obligation to update any such forward-looking statements in this document to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless required by law or regulation. Celyad Oncology Contacts: Investor Contact:Media Contact:David GeorgesVP Finance and Administrationinvestors@celyad.comCaroline LonezR&D Communications and Business Developmentcommunications@celyad.com Source: Celyad Oncology SA

细胞疗法临床1期免疫疗法

2022-12-13

·佰傲谷BioValley

异体γδ CAR-T疗效持续性遭质疑，Adicet Bio股价腰斩

近日（12月10日），Adicet Bio报告了其在研CAR-T疗法ADI-001的I期临床积极结果。ADI-001是一款同种异体γ δ CAR-T，目前处于I期临床阶段，被开发用于复发或难治性B细胞非霍奇金淋巴瘤的治疗。ADI-001通过抗CD20 CAR，γ δ T细胞受体和T细胞内源性细胞毒性受体靶向恶性B细胞。临床前研究显示，用抗CD20修饰的γ δ T细胞具有显著的抗肿瘤活性。本次研究是一项开放标签，多中心的I期临床，纳入了被诊断患有B细胞恶性肿瘤，复发或对至少两种既往疗法难治的成年患者。本研究的主要目标是评估ADI-001的安全性，耐受性，药动和药效特点，并确定单药治疗的最佳剂量。研究预计共招募75名受试者。截至2022年12月5日，16例可供评估的患者里，3人接受DL1（3千万CAR+细胞），3人接受DL2（1亿CAR+细胞），3人接受DL3（3亿CAR+细胞），1人在接受过一次淋巴细胞清除后，接受两剂DL3（2x3亿CAR+细胞，第一天和第七天），6人接受DL4（10亿CAR+细胞）。探索性基础上，本次研究主要是为了了解第二剂ADI-001的安全性和药代动力学特征，DL3剂量下第一和第二名患者在MRD为阴性且CR后，分别于第一剂后3个月和2个月接受了第二剂DL3剂量的ADI-001。参加本次研究的患者都接受过大量预处理，既往接受过的治疗中位数为4（2-6），根据国际预后指数（IPI）中位数分析，患者预后前景较差。研究结果显示，在所有剂量水平下ADI-001的ORR为75%，CR为69%。值得注意的是，在5名之前接受过自体CD19 CAR-T治疗并复发的大B细胞淋巴瘤（LBCL）患者中，ADI-001的 ORR和CR为100%。这些患者包括一名三打击高级别淋巴瘤患者，三名弥漫性大B细胞淋巴瘤（DLBCL）患者和一名双打击高级别淋巴瘤患者。此外，ADI-001治疗还在此前接受自体CAR-T疗法时达到PR的患者中达到了CR。DL3及以上剂量下，LBCL患者的CR为86%（6/7）.所有剂量水平下LBCL患者的CR为75%（9/12）。DL2和DL3的6个月CR率为33%；DL4将继续进行随访，以观察6个月时的疗效持久性。DL4下，患者外周血中循环的ADI-001细胞最多存在到第28天。本次研究中ADI-001具有良好的耐受性，没有出现剂量限制毒性，移植物抗宿主病（GvHD），三级或以上细胞因子风暴（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）。虽然Adicet Bio对于此次研究结果表示乐观，并计划与美国和欧盟监管机构就疗法注册问题进行讨论，但市场反应悲观，原因主要是本次临床研究中，该疗法在DL2和DL3下，6个月的CR仅为33%，疗效持续性存疑。消息发出后，公司Adicet Bio股价迎来腰斩。参考资料：1.https://investor.adicetbio.com/news-releases/news-release-details/adicet-bio-reports-positive-data-ongoing-adi-001-phase-1-trial近期热门视频更多精彩视频，尽在佰傲谷视频号，欢迎关注~本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处﹀点亮在看，传递信息♥

细胞疗法免疫疗法临床1期临床结果

100 项与 CYAD-01(Dartmouth College) 相关的药物交易

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研发状态

适应症	最高研发状态	国家/地区	公司
急性髓性白血病	临床2期	美国更多	Celyad Oncology SA 更多
骨髓增生性疾病	临床2期	比利时更多	Celyad Oncology SA 更多
骨髓增生异常综合征	临床2期	-	Dartmouth College 更多
多发性骨髓瘤	临床2期	美国更多	Celyad Oncology SA 更多
结直肠癌	临床1期	美国更多	Celyad Oncology SA 更多

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临床结果

适应症

分期

评价

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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


NCT03018405 (THINK trial, EHA2019)	临床1期	急性髓性白血病 NKG2D	-	CYAD-01 CAR-T cells	(膚醖願觸鏇簾廠糧窪範) = 3 injections at weekly intervals enhanced the anti-tumor efficacy of CYAD-01 T cells, resulting in 4-fold increase in animal survival compared to control, untreated animals 壓構顧簾遞襯衊遞齋繭 (廠構構壓繭廠鑰廠鹹顧 ) 更多	-	2019-06-15
P056 (EBMT2019)	N/A	血液肿瘤 NKG2D receptor \| NKG2D ligands	-	NKG2D-CAR T cells	(構襯餘窪淵憲夢簾遞夢) = increased cell proliferation up to 4 times 餘齋顧廠構繭選憲鬱繭 (餘遞製築繭淵繭醖壓網 ) 更多	积极	2019-03-24
NCT03018405 (THINK, GlobeNewswire) 人工标引	临床1期	复发性急性髓细胞白血病 \| 骨髓增生异常综合征	20	CYAD 01	蓋壓鑰製餘襯築遞觸選(餘廠夢築製觸憲衊簾鏇) = 壓遞鬱選廠鏇窪遞餘壓齋獵鑰廠遞鬱網鑰壓淵 (窪築獵蓋願醖鹽夢簾觸 ) 更多	积极	2019-06-17
NCT03018405 (ASH2018) 人工标引	临床1期	难治性急性髓细胞白血病	12	CYAD-01	(簾築願鑰襯夢淵膚齋衊) = 5 pts [in DL-1, one pt experienced G3 lymphopenia and a second pt experienced G4 lymphopenia and G4 pneumonitis in DL-2, one pt experienced G3 lymphopenia and G3 thrombocytopenia and two other pts experienced G3 cytokine release syndrome (CRS)] 願夢膚鑰積繭憲糧顧夢 (窪憲鹹繭鹹壓網襯鬱襯 )	积极	2018-11-29
NCT03466320 (Deplethink, ASH2019) 人工标引	临床1期	急性髓性白血病 \| 骨髓增生异常综合征	9	CYAD-01 1x108 cells/inf	(蓋顧壓壓淵夢膚蓋鹽窪) = At DL1,3 patients experienced grade (G) 1 toxicity (cytokine release syndrome or CRS and diarrhea), or G2 CRS ,. One other patient experienced G1 CRS during the second cycle. At DL2, only 1 patient experienced G1 related AEs (diarrhea and CRS) after the first CYAD-01 infusion. Another patient experienced G3 CRS during the second cycle. 願夢鑰醖遞製製糧遞糧 (艱鑰遞壓窪蓋壓鬱淵糧 )	积极	2019-11-13
NCT03466320 (Deplethink, ASH2019) 人工标引	临床1期	急性髓性白血病 \| 骨髓增生异常综合征	9	CYAD-01 3x108 cells/inf		积极	2019-11-13