A Phase I Clinical Study of Autologous T cells modified with chimeric antigen receptor targeting EpCAM ( EPCAM CAR-T) in Patients with malignant tumors of the digestive system (including advanced gastric cancer, colorectal cancer, liver cancer and pancreatic cancer) .

开始日期2021-09-30

申办/合作机构

浙江大学

NCT02915445

/ Active, not recruiting临床1期IIT

T Cells Armed With Chimeric Antigen Receptor Recognizing EpCAM for Patients With Advanced Solid Tumors

This study is for patients that have nasopharyngeal carcinoma, breast cancer, gastric cancer and other solid tumors. As epithelial cell adhesion molecule (EpCAM) is a well characterized molecule that is closely with poor prognosis and tumor metastasis and invasion. Many therapies targeting EpCAM have shown benefits for cancer patients. This study is to determine the safety of the engineered T cells armed with chimeric antigen receptor (CAR-T) recognizing EpCAM. At the same time, efficacy is to be evaluated by the criteria of RECIST. The EpCAM CAR-T were produced by lentiviral transduction of the novel 2nd generation of CAR genes. Different cohorts of patients receive EpCAM CAR-T with a dose-escalating manner. This study is to find the largest dose of EpCAM CAR-T, to learn what the adverse effects are and to find out whether this experimental intervention might help patients with nasopharyngeal carcinoma, breast cancer and other EpCAM positive solid tumors.

开始日期2016-07-01

申办/合作机构

四川大学

100 项与 IMC-001(Immunofoco Biotech) 相关的临床结果

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100 项与 IMC-001(Immunofoco Biotech) 相关的转化医学

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100 项与 IMC-001(Immunofoco Biotech) 相关的专利（医药）

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项与 IMC-001(Immunofoco Biotech) 相关的文献（医药）

2025-08-01·MOLECULAR THERAPY

Preclinical development and a phase 1 trial of IMC001, an EpCAM-targeted CAR-T cell therapy, in patients with advanced gastric cancer

Article

作者: Zhang, Shuangshuang ; Ge, Jingyu ; Yin, Weiwei ; Sun, Minmin ; Hao, Ruidong ; Fang, Weijia ; Luo, Tianhang ; Zheng, Rui ; Lu, Zhengmao

Autologous EpCAM-targeted CAR-T cell therapy (IMC001) was developed for advanced gastric cancer (GC). This study evaluated the specificity, efficacy, and safety of IMC001 in preclinical models and a phase 1 dose-escalation/expansion trial in patients who had failed at least two lines of therapy. IMC001 specifically recognized EpCAM and exhibited potent anti-tumor activity in EpCAM⁺ tumor cells, xenograft models, and patient-derived organoids. From August 2021 to May 2023, 12 advanced GC patients received IMC001. All patients experienced grade 3 or 4 treatment-related adverse events, mainly lymphopenia related to lymphodepletion, with no treatment-related deaths. Five patients experienced cytokine release syndrome (n = 3, grade 3-4) and two patients experienced immune-related hepatitis (n = 1, grade 3 in middle-dose group; n = 1, grade 4 in high-dose group). Partial responses were observed in 33.3% (1/3) of low-dose patients and 40% (2/5) of middle-dose patients, achieving an objective response rate of 30% and a disease control rate of 70%. Median progression-free survival and overall survival were 4.5 and 8.4 months, respectively. One patient underwent conversion surgery at week 27 and remains alive 31.5 months post-infusion. These findings demonstrate an acceptable safety profile and promising efficacy of IMC001 in advanced GC, supporting further clinical development for refractory GC patients.

2021-11-01·Clinical cancer research : an official journal of the American Association for Cancer Research1区 · 医学

Rapamycin Pretreatment Rescues the Bone Marrow AML Cell Elimination Capacity of CAR-T Cells

1区 · 医学

Article

作者: Fu, Binqing ; Wei, Haiming ; Nian, Zhigang ; Du, Xianghui ; Sun, Rui ; Dou, Yingchao ; Zheng, Xiaohu ; Tian, Zhigang ; Zhou, Li

Abstract:

Purpose::

Ongoing clinical trials show limited efficacy for Chimeric antigen receptor (CAR) T treatment for acute myeloid leukemia (AML). The aim of this study was to identify potential causes of the reported limited efficacy from CAR-T therapies against AML.

Experimental Design::

We generated CAR-T cells targeting Epithelial cell adhesion molecule (EpCAM) and evaluated their killing activity against AML cells. We examined the impacts of modulating mTORC1 and mTORC2 signaling in CAR-T cells in terms of CXCR4 levels. We examined the effects of a rapamycin pretreatment of EpCAM CAR-T cells (during ex vivo expansion) and assessed the in vivo antitumor efficacy of rapamycin-pretreated EpCAM CAR-T cells (including CXCR4 knockdown cells) and CD33 CAR-T cells in leukemia xenograft mouse models.

Results::

EpCAM CAR-T exhibited killing activity against AML cells but failed to eliminate AML cells in bone marrow. Subsequent investigations revealed that aberrantly activated mTORC1 signaling in CAR-T cells results in decreased bone marrow infiltration and decreased the levels of the rapamycin target CXCR4. Attenuating mTORC1 activity with the rapamycin pretreatment increased the capacity of CAR-T cells to infiltrate bone marrow and enhanced the extent of bone marrow AML cell elimination in leukemia xenograft mouse models. CXCR4 knockdown experiments showed that CXCR4 contributes to the enhanced bone marrow infiltration capacity of EpCAM CAR-T cells and the observed reduction in bone marrow AML cells.

Conclusions::

Our study reveals a potential cause for the limited efficacy of CAR-T reported from current AML clinical trials and illustrates an easy-to-implement pretreatment strategy, which enhances the anti-AML efficacy of CAR-T cells.See related commentary by Maiti and Daver, p. 5739

2020-08-01·Journal for immunotherapy of cancer2区 · 医学

Anti-tumor effects of NK cells and anti-PD-L1 antibody with antibody-dependent cellular cytotoxicity in PD-L1-positive cancer cell lines

2区 · 医学

ArticleOA

作者: Kim, Dong-Wan ; Kim, Soyeon ; Park, Ha-Ram ; Kim, Seong-Eun ; Keam, Bhumsuk ; Park, Ji-Eun ; Kim, Miso ; Kim, Tae Min ; Doh, Junsang ; Heo, Dae Seog

Background:

Although programmed cell death-1/programmed death-ligand 1 (PD-L1) inhibitors show remarkable antitumor activity, a large portion of patients with cancer, even those with high PD-L1-expressing tumors, do not respond to their effects. Most PD-L1 inhibitors contain modified fragment crystallizable region (Fc) receptor binding sites to prevent antibody-dependent cellular cytotoxicity (ADCC) against PD-L1-expressing non-tumor cells. However, natural killer (NK) cells have specific antitumor activity in the presence of tumor-targeting antibody through ADCC, which could enhance NK cell-induced cytotoxicity. We evaluated the antitumor efficacy of ADCC via anti-PD-L1 monoclonal antibodies (mAbs) and NK cells against several PD-L1-positive cancer cell lines.

Methods:

Various cancer cell lines were used as target cell lines. Surface PD-L1 expression was analyzed by flow cytometry. IMC-001 and anti-hPD-L1-hIgG1 were tested as anti-PD-L1 mAbs with ADCC and atezolizumab as an anti-PD-L1 mAb without ADCC. NK cell cytotoxicity was measured by 51Cr-release assay and CD107a degranulation assay. Also, live cell imaging was performed to evaluate cytotoxicity in a single-cell level. NK-92-CD16 (CD16-transduced NK-92 cell line) and peripheral blood mononuclear cells from healthy donors, respectively, were used as an effector cell. FcγRIIIa (CD16a)-V158F genotyping was performed for healthy donors.

Results:

We demonstrated that the cytotoxicity of NK-92-CD16 cells toward PD-L1-positive cancer cell lines was significantly enhanced in the presence of anti-PD-L1 mAb with ADCC. We also noted a significant increase in primary human NK cell cytotoxicity against PD-L1-positive human cancer cells when cocultured with anti-PD-L1 mAb with ADCC. Moreover, NK cells expressing a FCGR3A high-affinity genotype displayed higher anti-PD-L1 mAb-mediated ADCC lysis of tumor cells than donors with a low-affinity genotype.

Conclusion:

These results suggest that NK cells induce an ADCC response in combination with anti-PD-L1 mAbs, which helps promote ADCC antitumor activity against PD-L1-positive tumors. This study provides support for NK cell immunotherapy against high PD-L1-expressing tumors in combination with ADCC through anti-PD-L1 mAbs.

项与 IMC-001(Immunofoco Biotech) 相关的新闻（医药）

2025-08-25

·细胞基因治疗前沿

EpCAM靶向CAR-T疗法IMC001：晚期胃癌的新希望

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。近日，由上海长海医院、浙江大学附属第一医院和苏州易慕峰公司在《Molecular Therapy》发表了题为“Preclinical development and a phase I trial of IMC001, an EpCAM-targeted CAR-T cell therapy, in patients with advanced gastric cancer”的文章，EpCAM CAR-T治疗晚期胃癌的临床I期数据。 EpCAM（Epithelial Cell Adhesion Molecule，上皮细胞黏附分子），也称为CD326，在多种恶性肿瘤中均有显著表达，包括胃癌、结直肠癌、前列腺癌、卵巢癌、肺癌和胰腺癌。EpCAM在正常组织中表达有限，主要局限于某些上皮细胞的基底侧膜，例如结肠、小肠、肝前体细胞和胆管等。这种表达模式使得EpCAM在正常组织中不易被大型治疗分子（如CAR-T细胞）接触，因为它被紧密连接（tight junctions）限制。 IMC001是一种自体EpCAM靶向的第二代CAR-T细胞疗法，CAR结构包括人源化HuC215 scFv（针对EpCAM）、CD28跨膜和胞内共刺激域，以及CD3ζ信号域。小结 IMC001作为一种新型CAR-T细胞疗法，代表了实体瘤治疗领域的重要突破，在晚期胃癌中显示可管理安全性（中剂量推荐）和有前景疗效（ORR 30%，DCR 70%，可能手术转换）。通过靶向EpCAM这一特异性分子，IMC001有望克服实体瘤治疗中的关键障碍，为晚期胃癌患者提供新的治疗选择。未来的研究将进一步优化CAR-T细胞设计，探索联合治疗策略，并扩大适用患者群体。

细胞疗法免疫疗法临床1期

2025-08-14

·同写意

易慕峰实体瘤CAR-T发表最新研究成果 | 会员动态

免疫疗法细胞疗法临床1期

2025-05-27

·佰傲谷BioValley

ASCO 2025丨实体瘤CAR-T临床进展

ASCO 2025快要开始了，各类摘要也在陆续发布。小编其实是看到科济发布的Claudin18.2 CAR-T ASCO 2025摘要，然后突然想了解一下实体瘤CAR-T们的进展，便在ASCO网站上进行了一番检索。关于实体瘤CAR-T的ASCO 2025摘要并不多，有临床数据的也寥寥，以中国公司为主要研发力量，包括科济生物、易慕峰、斯丹赛、上海细胞治疗集团。（内容如有错漏，欢迎评论留言指正！）科济的CT041科济的Claudin18.2 CAR-T CT041（舒瑞基奥仑赛注射液）在业内很有名，是全球进度最快的实体瘤CAR-T管线。日前，科济在ASCO网站上发布了CT041在中国开展的针对晚期胃癌/食管胃结合部癌的II期临床试验（CT041-ST-01, NCT04581473）的研究结果摘要，报告了II期关键试验的主要结果。值得注意的是，这是全球范围内实体瘤CAR-T领域首个开展的确证性随机对照试验。从2022年3月29日至2024年8月16日，共有156例受试者被随机分配至CT041组（n=104）或TPC组（n=52）。其中，TPC组中有20例受试者接受了后续的CT041治疗。在ITT即所有随机人群中：基于IRC评价，CT041较标准治疗可显著延长PFS（mPFS 3.25个月 vs 1.77个月），达到试验的主要终点，患者疾病进展/死亡风险显著下降达63%。同时，OS显示出明显的获益趋势（mOS 7.92个月 vs 5.49个月）。在mITT即实际用药人群中：两组接受试验药物的受试者共136例，其中CT041组88例和TPC组48例。CT041组和TPC组基于IRC评价的mPFS为4.37个月 vs 1.84个月，患者疾病进展/死亡风险下降70%；mOS为8.61个月 vs 5.49个月，死亡风险下降40%。另外，TPC组20例接受CT041输注受试者的mOS达到9.20个月。两组所有接受CT041输注的108例受试者（其中CT041组88例，TPC组20例）mOS达9.17个月，而TPC组28例未使用CT041治疗者mOS仅3.98个月。安全性方面，整体耐受性良好，仅4例发生3级细胞因子释放综合症（CRS），无4-5级CRS，无任何免疫效应细胞相关神经毒性综合征（ICANS）发生。易慕峰的EpCAM CAR-T易慕峰在去年的ASCO 2024年会上展示了两款实体瘤CAR-T（IMC001和IMC002）的进展，今年也没缺席，但仅报告了一款EpCAM CAR-T IMC002的1期临床数据，该研究旨在评估EpCAM CAR-T在胃肠道癌症（包括胃癌和结直肠癌）患者中的安全性和有效性。截止2023年4月30日，共有25例患者接受了肿瘤组织中EpCAM表达的筛选，其中4例患者因EpCAM低表达而被排除在外。8例CRC患者和13例GC患者接受EpCAM CAR-T治疗。结果显示：EpCAM CAR-T显示出良好的安全性，在4周的随访中没有与治疗相关的死亡。高剂量组的2例患者（4.8%）出现DLT，9例患者（43%）出现1-3级CRS。在胃癌中观察到有希望的疗效，总缓解率（ORR）为23.5%，疾病控制率（DCR）为70.6%。同时，该研究结果还强调了抗原呈递和自然杀伤T细胞激活在介导CAR-T治疗反应中的重要性。斯丹赛的非病毒GCC19CART斯丹赛披露了其实体瘤CAR-T候选药物GCC19CART在美国的1期临床研究的早期数据。GCC19CART是斯丹赛基于实体瘤通用CoupledCAR®平台技术开发的首款临床候选管线。GCC19CART靶向GCC（GCC在原发性结直肠癌(CRC)细胞中稳定表达，在转移性CRC细胞中表达升高，是CRC的特异性标志分子），被开发用于治疗复发/难治性转移性CRC。GCC19CART正在中国和美国进行临床研究。本次更新了美国1期临床的数据，该研究旨在评估GCC19CART在美国CRC患者的安全性和有效性。截止2025年1月23日，有9名患者接受GCC19CART治疗。所有受试者均发生CRS（1-2级）；2/9发生免疫效应细胞相关神经毒性综合征；DL2中1名患者出现剂量限制性毒性，并在输注后48天死亡。DL1中（n=4）的ORR为25%（1/4 PR）；DL2（n=5）的ORR为80%（4/5 3例PR和1例病理完全缓解）。DL1的PR在第2个月达到，而DL2中3/4的PR在第1个月达到，表现出剂量依赖性的肿瘤杀伤活性。DL2中有2例患者在数据截止时保持缓解；1例患者在2个月时通过PET获得完全代谢反应，并在第6个月通过CT维持PR，肿瘤持续缩小（第1个月：38.33%，第2个月：40.77%，第4个月：82.58%，第6个月：75.61%）；另1例患者在6个月时保持PR，并在8个月时进展。DL1的中位无进展生存期（PFS）为5.0个月，DL2为7.8个月。DL1的中位缓解持续时间为2.2个月，DL2的中位缓解持续时间为6.9个月。研究报告，与之前在中国的试验相比，美国研究表明GCC19CART的安全性和有效性存在提高的潜在趋势。上海细胞治疗集团的非病毒MSLN CAR-T上海细胞治疗集团发布的一份ASCO摘要，报告了其基于JL-Lightning™无培养超快速非病毒CAR-T制备平台开发的、自分泌PD-1纳米抗体的、靶向MSLN的自体CAR-T（自体非病毒aPD1-MSLN JL-lightning-CAR-T）候选药物BZT2312的1期初步数据。JL-Lightning™无培养超快速非病毒CAR-T制备工艺，能够增强CAR-T干性、体内扩增和持久性，而且BZT2312仅需30个小时即可制备完成。BZT2312的1期研究招募了标准治疗失败且通过IHC证实MSLN和PD-L1在肿瘤上表达的恶性胸膜间皮瘤（MPM）患者，旨在评估BZT2312的安全性和有效性。入组7例晚期MPM患者，并接受单剂量CAR-T细胞输注。在DL1中，1例患者达到PR，DCR为75%（3/4）；DL2中，3例患者达到ORR（100%，3/3），其中1例患者在3个月时达到CR并维持9个月以上。安全性方面：DL1中，4例患者中有1例观察到CRS（1级），无ICANS或DLT。DL2中，3例患者中有2例观察到CRS（3-4 级），无 ICANS；2例发生3级免疫介导的肺炎，通过临床干预策略进行管理。所有患者均出现3-4级血液学毒性，在支持治疗下可逆。A2 Bio的逻辑门CAR-TA2 Biotherapeutics (A2 Bio) 是一家美国的临床阶段细胞治疗公司，致力于基于该公司专有的Tmod™平台开发逻辑门控细胞疗法，以选择性地靶向肿瘤细胞并保护正常细胞。A2 Bio在ASCO 2025年会上发布了两份摘要，分别报告了两款Tmod CAR-T候选药物的早期临床数据。CEA Tmod CAR-TA2B530是基于Tmod™平台开发的CEA靶向的逻辑门控CAR-T，其通过靶向CEA的CAR激活受体和识别HLA-A*02的阻断受体来区分肿瘤细胞和正常细胞。A2B530的临床研究EVEREST-1，筛选表达CEA和HLA杂合性缺失（HLA LOH）的不可切除的局部晚期或转移性实体瘤患者入组。截止2025年1月15日，共有14名患者入组。结果显示，耐受性良好，中性粒细胞减少症在第7-10天达到最低点，所有患者均恢复，并且没有明显的长时间血细胞减少发作。没有剂量限制性毒性、>3级严重不良事件（AEs）或相关神经毒性发作。DL2的1名患者经历了可能的2级CRS，从第15天开始，并在2天内通过支持治疗消退；后来CRS诊断被参与者中心线的阳性血培养所混淆。CRS的低发生率与输注后28天内测得的低水平血清细胞因子一致。A2B530显示出潜在的临床疗效和剂量反应。DLs1-2中的6名参与者已完成集中反应评估，3名胰腺癌（PANC）患者观察到1名部分缓解；峰扩展显示可能的剂量反应。MSLN Tmod CAR-TA2B694是基于Tmod™平台开发的MSLN靶向的逻辑门控CAR-T，其通过靶向MSLN的CAR激活受体和识别HLA-A*02的阻断受体来区分肿瘤细胞和正常细胞。A2B694正在进行临床研究EVEREST-2，筛选表达MSLN和HLA LOH的复发性不可切除的局部晚期或转移性实体瘤患者入组。截止2025年1月15日，共有5名患者入组。研究报告，耐受性良好，没有剂量限制性毒性、CRS，也没有相关的神经毒性。1名参与者因食欲下降而入院。输注后7.5个月内未发现长期毒性。在接受A2B694治疗的参与者中，5名在DLs1 -2时可评估疗效。所有患者输注后外周血均检测到A2B694。此外，输注42天时的胰腺癌患者的腹部肿瘤活检中检测到A2B694。小结实际上，实体瘤CAR-T的面临着诸多挑战，包括肿瘤抗原的异质性、实体瘤免疫抑制微环境、脱靶效应、CAR‑T细胞难以归巢和T细胞衰竭等。许多公司正在通过不同的技术手段来克服这些挑战，但是进展都不是很顺。而国内在实体瘤CAR-T的研究上，站在全球领先地位。参考资料：1.https://www.asco.org/abstracts-presentations/ABSTRACT4927722.科济生物《科济药业舒瑞基奥仑赛注射液（CT041）的摘要已公布于ASCO网站》3.https://www.asco.org/abstracts-presentations/ABSTRACT4955844.https://www.asco.org/abstracts-presentations/ABSTRACT5090965.https://www.asco.org/abstracts-presentations/ABSTRACT4944846.https://www.asco.org/abstracts-presentations/ABSTRACT5035987.https://www.asco.org/abstracts-presentations/ABSTRACT503930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········

ASCO会议免疫疗法细胞疗法临床1期临床结果

100 项与 IMC-001(Immunofoco Biotech) 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
晚期结直肠腺癌	临床1期	中国	浙江大学	2021-09-30
晚期胃癌	临床1期	中国	浙江大学	2021-09-30
晚期肝细胞癌	临床1期	中国	浙江大学	2021-09-30
胰腺癌	临床1期	中国	浙江大学	2021-09-30
晚期恶性实体瘤	临床申请批准	中国	苏州易慕峰生物科技有限公司	2025-03-21
消化系统肿瘤	临床申请批准	美国	苏州易慕峰生物科技有限公司	2024-02-23

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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


NEWS 人工标引	N/A	胃癌	10	IMC001	網鑰觸糧簾鹽衊餘蓋鹹(壓餘構遞廠艱遞淵齋獵) = 鹹壓鑰鏇鹽構餘膚餘簾膚築範積網鑰憲顧餘鹽 (餘憲選夢鏇觸網窪遞願 ) 更多	积极	2024-12-29
ChiCTR2100047129 \| NCT05028933 (ESMO2022) 人工标引	早期临床1期	结直肠癌 \| 胃癌 EpCAM	10	IMC001 3×10ˆ5 cells/kg	積餘鏇廠壓鹹鹹憲觸淵(積鑰憲鹹築網艱網艱鬱) = 壓構鹽繭醖憲齋餘壓鹹壓製繭餘壓鑰繭蓋齋製 (醖衊製艱憲觸鹹繭構網 ) 更多	积极	2022-09-10