A Phase I/II Study of IMCnyeso, HLA- A*0201-Restricted, NY-ESO-1- and LAGE-1A-specific Soluble T Cell Receptor and Anti-CD3 Bispecific Molecule, in HLA-A*0201 Positive Patients With Advanced NY-ESO-1 and/or LAGE - 1A Positive Cancer

IMCnyeso is a bispecific fusion protein designed for the treatment of cancers that express NY-ESO-1 and/or LAGE-1A. This was a first-in-human trial designed to evaluate the safety and efficacy of IMCnyeso in HLA-A*02:01-positive adult participants whose cancer is positive for NY-ESO-1 and/or LAGE-A1.

开始日期2018-06-15

申办/合作机构

Immunocore Ltd.

NCT02737787 / Completed临床1期IIT

A Phase I Study of Concomitant WT1 Analog Peptide Vaccine or NY-ESO-1 Overlapping Peptides Vaccine in Combination With Nivolumab in Patients With Recurrent Ovarian Cancer Who Are in Second or Greater Remission

The purpose of this study is to test the safety of a combination of an investigational WT1 vaccine and another drug called nivolumab. This is the first time that the WT1 vaccine and nivolumab are being used in combination. Also, to test the safety of a combination of an investigational NY-ESO-1 vaccine and another drug called nivolumab.

开始日期2016-04-01

申办/合作机构

Memorial Sloan Kettering Cancer Center

NCT01795976 / Terminated临床2期

A Phase II Trial to Assess the Activity of NY-ESO-1 Targeted T Cells in Advanced Oesophagogastric Cancer

This is a trial of adoptive T cell therapy using the patient's own T cells, genetically engineered to target the tumour associated antigen NY-ESO-1 (New York esophageal squamous cell carcinoma 1). Eligible patients will undergo leukapheresis (a process to remove white blood cells) to retrieve sufficient T cells which will be gene modified and expanded in the laboratory. Patients will undergo preconditioning chemotherapy with cyclophosphamide (60mg/kg) day -7 and day -6, followed by fludarabine (25mg/m2) day -5 to day -1. The NY-ESO-1 gene modified cells will be re-infused on day 0 and the patients will receive up to 14 doses of intravenous Interleukin2 (100000 U/kg) from day 0 to day 4.
The primary objective of response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria will be assessed by CT scans carried out at week 6, week 12 and at 12 weekly intervals thereafter.

开始日期2014-10-01

申办/合作机构

The Christie Pathology Partnership LLP

[+6]

100 项与 IMC-nyeso(Immunocore Ltd.) 相关的临床结果

登录后查看更多信息

100 项与 IMC-nyeso(Immunocore Ltd.) 相关的转化医学

登录后查看更多信息

100 项与 IMC-nyeso(Immunocore Ltd.) 相关的专利（医药）

登录后查看更多信息

187

项与 IMC-nyeso(Immunocore Ltd.) 相关的文献（医药）

2023-10-01·Cancer immunology, immunotherapy : CII

Oncolytic attenuated measles virus encoding NY-ESO-1 induces HLA I and II presentation of this tumor antigen by melanoma and dendritic cells.

Article

作者: Berland, Laurine ; Deshayes, Sophie ; Boisgerault, Nicolas ; Tangy, Frédéric ; Blanquart, Christophe ; Labarrière, Nathalie ; Arbabian, Atousa ; Chatelain, Camille ; Fradin, Delphine ; Combredet, Chantal ; Grard, Marion ; Idjellidaine, Mohamed ; Fonteneau, Jean-François ; Dehame, Virginie ; Dutoit, Soizic

Antitumor virotherapy stimulates the antitumor immune response during tumor cell lysis induced by oncolytic viruses (OVs). OV can be modified to express additional transgenes that enhance their therapeutic potential. In this study, we armed the spontaneously oncolytic Schwarz strain of measles viruses (MVs) with the gene encoding the cancer/testis antigen NY-ESO-1 to obtain MVny. We compared MV and MVny oncolytic activity and ability to induce NY-ESO-1 expression in six human melanoma cell lines. After MVny infection, we measured the capacity of melanoma cells to present NY-ESO-1 peptides to CD4 + and CD8 + T cell clones specific for this antigen. We assessed the ability of MVny to induce NY-ESO-1 expression and presentation in monocyte-derived dendritic cells (DCs). Our results show that MVny and MV oncolytic activity are similar with a faster cell lysis induced by MVny. We also observed that melanoma cell lines and DC expressed the NY-ESO-1 protein after MVny infection. In addition, MVny-infected melanoma cells and DCs were able to stimulate NY-ESO-1-specific CD4 + and CD8 + T cells. Finally, MVny was able to induce DC maturation. Altogether, these results show that MVny could be an interesting candidate to stimulate NY-ESO-1-specific T cells in melanoma patients with NY-ESO-1-expressing tumor cells.

2023-06-02·Medicine

Involvement of NY-ESO-1 and MAGE-A4 in the pathogenesis of desmoid tumors.

Article

作者: Akagi, Masao ; Nishimura, Shunji ; Kakinoki, Ryosuke ; Shinyashiki, Yu ; Ito, Tomohiko ; Hashimoto, Kazuhiko

The involvement of New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma-associated antigen A4 (MAGE-A4) in soft-tissue sarcoma pathogenesis has recently been reported; however, their involvement in desmoid tumors (DTs) remains unknown. This study aimed to determine the involvement of NY-ESO-1 and MAGE-A4 in DTs. Immunostaining for β-catenin, NY-ESO-1, and MAGE-A4 was performed on DT biopsy specimens harvested at our institution. The positivity rate for each immune component was calculated. In addition, the correlations between the positivity rates for the immune molecules were investigated. The correlation between the positivity rate and age or longest diameter of each immune molecule was also investigated. β-catenin showed staining mainly in the tumor cell nuclei of DTs. Both NY-ESO-1 and MAGE-A4 showed staining in the nucleus, cytoplasm, and infiltrating lymphocytes of DT cells. The mean positive cell rates for β-catenin, NY-ESO-1, and MAGE-A4 were 43.9 ± 21.7, 30 ± 21.6, and 68.9 ± 20.8, respectively. A strong negative correlation was observed between β-catenin and MAGE-A4 positivity rates (r = -0.64). The positivity rates for NY-ESO-1 and MAGE-A4 showed a moderate positive correlation (r = -0.42). A very strong negative correlation was observed between age and the NY-ESO-1 positivity rate (r = -0.72). A weak negative correlation was observed between age and the MAGE-A4 positivity rate (r = -0.28). A medium negative correlation was observed between the longest tumor diameter and NY-ESO-1 positivity (r = -0.37). NY-ESO-1 and MAGE-A4 may be involved in the DT microenvironment. Thus, NY-ESO-1 and MAGE-A4 may be useful in the diagnosis of DT.

2023-03-31·Journal of translational medicine

Treatment with decitabine induces the expression of stemness markers, PD-L1 and NY-ESO-1 in colorectal cancer: potential for combined chemoimmunotherapy.

Article

作者: Uddin, Shahab ; Sahir, Fairooz ; Makni-Maalej, Karama ; Hydrose, Shereena ; Taib, Nassiba ; Mestiri, Sarra ; Nizamuddin, Parveen B ; Merhi, Maysaloun ; Azizi, Fouad ; Raza, Afsheen ; Al-Zaidan, Lobna ; Maccalli, Cristina ; Dermime, Said ; Yoosuf, Zeenath Safira K M ; Almoghrabi, Salam ; Inchakalody, Varghese ; Shablak, Alaaeldin ; Fernandes, Queenie ; Al Homsi, Mohammed Ussama

BACKGROUND:

The mechanism of tumor immune escape and progression in colorectal cancer (CRC) is widely investigated in-vitro to help understand and identify agents that might play a crucial role in response to treatment and improve the overall survival of CRC patients. Several mechanisms of immune escape and tumor progression, including expression of stemness markers, inactivation of immunoregulatory genes by methylation, and epigenetic silencing, have been reported in CRC, indicating the potential of demethylating agents as anti-cancer drugs. Of these, a chemotherapeutic demethylating agent, Decitabine (DAC), has been reported to induce a dual effect on both DNA demethylation and histone changes leading to an increased expression of target biomarkers, thus making it an attractive anti-tumorigenic drug.

METHODS:

We compared the effect of DAC in primary 1076 Col and metastatic 1872 Col cell lines isolated and generated from patients' tumor tissues. Both cell lines were treated with DAC, and the expression of the NY-ESO-1 cancer-testis antigen, the PD-L1 immunoinhibitory marker, and the CD44, Nanog, KLF-4, CD133, MSI-1 stemness markers were analyzed using different molecular and immunological assays.

RESULTS:

DAC treatment significantly upregulated stemness markers in both primary 1076 Col and meta-static 1872 Col cell lines, although a lower effect occurred on the latter: CD44 (7.85 fold; ***p = 0.0001 vs. (4.19 fold; *p = 0.0120), Nanog (4.1 fold; ***p < 0.0001 vs.1.69 fold; ***p = 0.0008), KLF-4 (4.33 fold; ***p < 0.0001 vs.2.48 fold; ***p = 0.0005), CD133 (16.77 fold; ***p = 0.0003 vs.6.36 fold; *p = 0.0166), and MSI-1 (2.33 fold; ***p = 0.0003 vs.2.3 fold; ***p = 0.0004), respectively. Interestingly, in the metastatic 1872 Col cells treated with DAC, the expression of both PD-L1 and NY-ESO-1 was increased tenfold (*p = 0.0128) and fivefold (***p < 0.0001), respectively.

CONCLUSIONS:

We conclude that the upregulation of both stemness and immune checkpoint markers by DAC treatment on CRC cells might represent a mechanism of immune evasion. In addition, induction of NY-ESO-1 may represent an immuno-therapeutic option in metastatic CRC patients. Finally, the combination of DAC and anti-PD-1/anti-PD-L1 antibodies treatment should represent a potential therapeutic intervention for this group of patients.

项与 IMC-nyeso(Immunocore Ltd.) 相关的新闻（医药）

2024-05-02

·GlobeNewswire-Health Care

Medigene AG Expands Patent Portfolio with European Patent Grant for its NY-ESO-1 – targeted T Cell Receptor

Planegg/Martinsried, May 2, 2024. Medigene AG (Medigene or the “Company”, FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, announces today that the Company has been issued a patent by the European Patent Office protecting its T cell receptor (TCR) targeting NY-ESO-1 (New York esophageal squamous cell carcinoma 1), a well-recognized and validated cancer-testis antigen, which is expressed in multiple tumor types. “We are delighted to announce the protection of our NY-ESO-1-targeted TCR in Europe. This TCR, together with the PD1-41BB costimulatory switch protein (CSP), serves as the main component of our lead program MDG1015. This patent grant adds to similar patents that were also granted in the United States, Japan, South Korea, Taiwan and Australia and reinforces the key technologies of our End-to-End Technology platform and its ability to generate optimal affinity 3S (sensitive, specific and safe) TCRs,“ said Selwyn Ho, CEO at Medigene AG. “Along with our differentiated TCR-T therapies for solid tumors, such as MDG1015, we are also exploring opportunities to expand the application of our potential best-in-class TCRs into other modalities such as T cell engagers (TCE) and TCR natural killer cell (TCR-NK) therapies.” Medigene continually extends and strengthens its patent portfolio with new technologies and expands existing patents into additional jurisdictions. The Company maintains over 20 different patent families worldwide covering applications protecting Medigene’s 3S TCRs as well as its exclusive E2E Platform technologies. --- end of press release --- About Medigene AG Medigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing differentiated T cell therapies for treatment of solid tumors. Its End-to-End Platform is built on multiple proprietary and exclusive technologies that enable the Company to generate optimal T cell receptors against both cancer testis antigens and neoantigens, armor and enhance these T cell receptor engineered (TCR) -T cells to create best-in-class, differentiated TCR-T therapies, and optimize the drug product composition for safety, efficacy and durability. The End-to-End Platform provides product candidates for both its own therapeutics pipeline and partnering. Medigene’s lead TCR-T program MDG1015 is expected to receive IND/CTA approval in the second half of 2024. For more information, please visit https://medigene.com/ About Medigene’s MDG1015 Program MDG1015 is a first-in-class, 3rd generation T cell receptor engineered T cell (TCR-T) therapy targeting NY-ESO-1/ LAGE-1a, a well-recognized and validated cancer testis antigen, which is expressed in multiple tumor types. MDG1015 contains our optimal affinity 3S (sensitive, specific and safe) NY-ESO-1/LAGE-1a TCR combined with our proprietary PD1-41BB costimulatory switch protein that blocks the PD1/PD-L1 inhibitory axis while simultaneously activating the T cell through the well described -41BB pathway further enhancing the activity and persistence of the TCR-T in the hostile tumor microenvironment. The Company expects IND/CTA approval for MDG1015 in the second half of 2024. This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene® is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only. Medigene AG Pamela Keck Phone: +49 89 2000 3333 01 E-mail: investor@medigene.com In case you no longer wish to receive any information about Medigene, please inform us by e-mail (investor@medigene.com). We will then delete your address from our distribution list.

免疫疗法细胞疗法

2024-04-17

·CPHI制药在线

潜在首款TCR-T疗法关键试验结果登《柳叶刀》，国内企业加速抢滩

关注并星标CPHI制药在线近日，Adaptimmune Therapeutics宣布其在研工程化T细胞疗法afami-cel的关键性2期临床研究SPEARHEAD-1的积极数据发表于《柳叶刀》当中。美国FDA已接受afami-cel的生物制品许可申请（BLA），并授予其优先审评资格。该申请的PDUFA日期为2024年8月4日。如果获得批准，afami-cel将成为首款用于治疗实体瘤的工程化T细胞疗法，也是十多年来治疗滑膜肉瘤的首个有效疗法。图片来源：参考来源1 共有52名患者在北美和欧洲的23个医疗中心参与了这项2期临床试验，其中44名滑膜肉瘤患者和8名黏液样圆细胞脂肪肉瘤（MRCLS）患者。36%的患者（19/52人）对治疗有反应，肿瘤缩小或在某些情况下完全消失。该疗法对滑膜肉瘤患者比对MRCLS患者更有效。平均而言，滑膜肉瘤患者的反应持续时间略高于11个月，而MRCLS患者的反应持续时间略高于4个月。大多数患者在癌症缓解一段时间后复发。目前为止，有少数在初始治疗后肿瘤消失的患者没有复发。在所有患者中，平均生存期略高于15个月，一年生存率为60%。在滑膜肉瘤患者中，肿瘤对初始治疗显示完全应答（即单次治疗后肿瘤完全消失），一年生存率为90%，两年生存概率为70%。该治疗最常见的副作用涉及红细胞和白细胞计数低，这是由于为准备身体接受工程T细胞所需的化疗所致。许多患者需要通过治疗来控制细胞因子释放综合征（即细胞因子风暴），这是T细胞疗法常见的副作用。在随访期间发生的28例死亡被证明均是由于癌症最终进展而非治疗所致。在这项国际性、开放标签的2期临床试验中，TCR-T细胞疗法afami-cel在晚期滑膜肉瘤和黏液样圆细胞脂肪肉瘤（MRCLS）患者中产生了持久缓解。这项临床试验表明，TCR-T细胞疗法可以有效地靶向实体瘤，并为将这种方法扩展到其他实体恶性肿瘤提供了理论基础。 Afami-cel是一款MAGE-A4靶向的TCR-T细胞疗法，MAGE-A4作为癌睾丸抗原，在多种肿瘤组织中高表达。尽管滑膜肉瘤和黏液样圆细胞脂肪肉瘤是两种不同的癌症，但它们具有共同的临床和生物学特征，它们都高表达癌-睾丸抗原（CT抗原），包括MAGE-A4和NY-ESO-1。该疗法从患者体内提取T细胞并使用慢病毒载体进行基因工程改造，表达靶向HLA-A*02呈递的MAGE-A4 230-239 GVYDGREHTV的高亲和力和特异性T细胞受体（TCR），该TCR引导T细胞靶向表达MAGE-A4的癌细胞并清除这些癌细胞。FDA已授予其治疗晚期软组织肉瘤的孤儿药资格（ODD）和晚期滑膜肉瘤的再生医学高级疗法（RMAT）资格。另外，Adaptimmune 还在开发下一代TCR-T疗法ADP-A2M4CD8，这种疗法与afami-cel的区别在于，这些细胞还表达CD8α共受体以及靶向MAGE-A4的工程TCR。其临床前数据表明，CD8α的共表达可以拓宽对实体瘤的免疫反应，并通过将CD4细胞转化为CD8杀伤细胞或细胞毒性T细胞来增加抗肿瘤活性，同时保留其CD4辅助功能；此外ADP-A2M4CD8针对MAGE-A4，MAGE-A4是在多种实体瘤类型中表达的癌症评估抗原的MAGE家族成员。目前A2M4CD8的1期SURPASS临床数据显示，疗效信号支持卵巢癌、尿路上皮癌和头颈癌的进一步发展。对于患有广泛表达MAGE-A4的不可切除或转移性肿瘤的患者（包括接受纳武利尤单抗（nivolumab）联合治疗的患者），ADP-A2M4CD8继续显示出可接受的风险效益。Adaptimmune临床实体瘤T细胞治疗管线图片来源：Adaptimmune官网喜中有忧的AdaptimmuneAdaptimmune Therapeutics是一家细胞疗法公司，致力于重新定义癌症治疗方法，尤其聚焦实体瘤治疗。公司独特的工程化T细胞受体（TCR）平台使T细胞工程能够靶向摧毁多种实体瘤类型的癌症。2023年3月，Adaptimmune和TCR2 Therapeutics共同宣布，两家公司将合并成为一家新公司，进一步巩固了Adaptimmune公司在TCR-T细胞疗法领域的地位。 Adaptimmune依托其独有的Spear-T细胞技术，是最早将TCR-T疗法推进临床试验的Biotech公司。Adaptimmune的技术曾先后得到葛兰素史克、安斯泰来、基因泰克等大药企的认可，建立了合作开发的关系，但遗憾的是，最后都无疾而终了。 • 2022年10月，葛兰素史克向Adaptimmune退还了靶向NY-ESO的TCR-T疗法的全部权益； • 2023年4月，安斯泰来宣布终止了与 Adaptimmune的TCR-T疗法研发合作，此前该合作项目总金额达8.975亿美元； • 2024年4月，基因泰克宣布终止了与Adaptimmune公司价值高达30亿美元的细胞疗法合作。两家公司最初计划开发针对最多五个癌症靶点的异体细胞疗法，同时建立一个个性化异体细胞疗法平台。除了与多个MNC的合作项目告吹外，Adaptimmune公司的股价在过去两年的跌幅较大还有其他原因： • 研发进度慢。主要资产afami-cel在递交上市进度方面较为拖拉，此前给出的预期是2021年上半年申报BLA，2022年上市，目前进度已经大为落后。 • 临床试验数据存在瑕疵。afami-cel此前发布的数据中，药物疗效的持久性存疑，入组患者中存在细胞因子释放综合征的现象，加剧了市场对药物能否获批的担忧。 • 适应症市场想象空间不足。滑膜肉瘤的发病率为2.75人/10万人，全美每年新增病例不足800人，作为一款二线疗法，afami-cel的销售潜力难以突破1亿美元。TCR-T疗法简介 TCR-T的全称是"T细胞受体工程化T细胞疗法"，同属新型细胞免疫疗法。主要通过基因编辑技术，将能特异性识别肿瘤抗原的T细胞受体（TCR）基因导入患者自身的T细胞内，使其表达外源性TCR，从而具有特异性杀伤肿瘤细胞的活性。 T淋巴细胞被誉为人体内的"战士"，在人体血液、淋巴和周围组织器官发挥免疫功能，能够抵御和消灭肿瘤细胞。但在肿瘤细胞逃逸过程中，T细胞却不能很好地识别杀伤肿瘤细胞。 TCR（T cell receptor）是T细胞表面的特异性受体，以非共价键与CD3结合，形成TCR-CD3复合物，通过识别并结合MHC呈递的抗原从而激活T细胞，促进T细胞的分裂与分化。TCR-T疗法是向正常外周血淋巴细胞上导入已知的抗原特异性TCR基因进行治疗的一种疗法。普通T细胞中引入新的基因，使得改造过的T细胞能够表达有效识别肿瘤细胞的TCR，从而引导T细胞杀死肿瘤细胞。目前在血液瘤领域大获成功的CAR-T，由于特异性靶标的掣肘，在实体瘤领域进展缓慢。而TCR-T识别的是多肽-MHC复合体，不仅精准、范围广泛，还更容易浸润到实体瘤内部，大大拓宽了肿瘤免疫治疗的靶点。针对单个抗原靶点的TCR-T回输后，可以进一步激活患者自身针对其他肿瘤抗原表位的T细胞，具有逆转实体瘤抑制性免疫微环境的作用，有望实现更好的疗效与持久性。与此同时，TCR-T只介导少量细胞因子的释放，在安全性上具有天然优势。总体而言，TCR-T将是实体瘤治疗领域极具威力的"杀手锏"国内药企争相布局TCR-T赛道 TCR-T 研发的星星之火，已渐成燎原之态，国内外众多企业布局 TCR-T 细胞治疗。2022 年 1 月，美国食品和药物管理局（FDA）已批准全球第一个 T 细胞受体（TCR）治疗药 Kimmtrak（IMCgp100）上市，用于治疗 HLA-A*02:01 阳性不可切除性或转移性葡萄膜黑色素瘤（mUM）成人患者，为TCR 疗法治疗实体瘤奠定基础。而今第一个 TCR-T 疗法的申报上市，意味着肿瘤治疗靶点从胞外转移到胞内，开辟了全新的靶点选择空间。根据美国临床试验注册库的数据，目前在研的 TCR-T 治疗实体瘤种类，主要包括转移性非小细胞肺癌、肝细胞癌、多发性骨髓瘤、软组织肉瘤、头颈癌、黑色素瘤、脂肪肉瘤和宫颈癌等，主要分布在美国和中国。在国内的 TCR-T 细胞治疗中，香雪制药、百吉生物、天科雅、普瑞金、深圳宾德、来恩生物、泛恩生物、华夏英泰、立凌生物、可瑞生物等多家药企布局了这一赛道。TCR-T疗法覆盖的肿瘤适应症图片来源：可瑞生物官网国内 TCR-T 细胞治疗企业与管线一览（部分）图片来源：医麦客香雪制药的TAEST16001是中国首个获批临床试验的TCR-T细胞疗法。2023年8月15日，国际著名期刊Cell Reports Medicine刊发了TAEST16001的1期临床研究成果，该产品适应症为软组织肉瘤，I期临床研究肿瘤客观缓解率（ORR）达到41.7%，中位无进展生存期（PFS）为7.2个月，中位缓解持续时间（DOR）为13.1个月，并已进入II期临床研究。来恩生物的First in class候选TCR-T疗法LioCyx-M004能够利用mRNA编码表达HBV抗原特异性的TCR来靶向肝癌细胞。2022年11月，来恩生物在2022年美国肝病研究协会年会上以海报形式公布了LioCyx-M004的1期临床试验数据，初步证明了该产品具有良好的靶向性和持久抗肿瘤作用。目前，LioCyx-M004正在进行2期临床试验。星汉德生物的SCG101通过引入病毒特异性TCR基因序列重定向T细胞，使其表达针对乙肝病毒表面抗原（HBsAg）的特异性T细胞受体，定向清除HBV感染的肝细胞和肝癌细胞，还可能调节肝脏中的免疫抑制微环境。值得一提的是，这是第一个在中国获批IND治疗肝癌的TCR-T细胞治疗药物。去年6月，星汉德生物在国际细胞与基因治疗学会（ISCT）会议上展示了SCG101的最新临床数据：单剂量SCG101输注后可根除100%的HBsAg+肝细胞，使得74.5%的肝肿瘤细胞减少。天科雅的TC-E202是一种加载抗PD-1抗体的TCR-T疗法，它在编码HPV16 E6 TCR的同时，编码抗PD-1的单链抗体可变区片段。经病毒转染，T细胞能够表达HPV16 E6 TCR并同时分泌抗PD-1的单链抗体，有效消除肿瘤微环境的抑制。当TC-E202输入患者体内，经改造的T细胞表面表达的TCR能有效识别宫颈癌肿瘤抗原HPV16 E6。目前TC-E202正在开展I/II期临床研究，旨在评估TC-E202在HPV16阳性的既往治疗失败的复发或转移性宫颈癌患者中的安全性和耐受性。参考来源 1. Sandra P D'Angelo,et al. Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial . doi.org/10.1016/S0140-6736(24)00319-2 2. 企业官网 3. Yating Liu, et al. TCR-T Immunotherapy: The Challenges and Solutions . Front Oncol. 2022 Jan 25;11:794183. 4. Estelle Baulu, et al. TCR-engineered T cell therapy in solid tumors: State of the art and perspectives. Sci Adv. 2023 Feb 15;9(7):eadf3700.【智药研习社近期直播预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

细胞疗法临床2期孤儿药临床1期临床结果

2024-04-17

·今日头条

新发现！中国科学院揭示促进TCR-T癌症免疫治疗的最新策略

本文为转化医学网原创，转载请注明出处作者：Rainbow 导读：基于抗原特异性T细胞受体工程T细胞(TCR-T)的免疫疗法已被证明是对抗癌症的有效方法。 4月13日，中国科学院研究团队在期刊《Cell Death & Disease》上在线发表题为“STING agonist diABZI enhances the cytotoxicity of T cell towards cancer cells”的研究论文，体外和体内数据表明，STING靶向和TCR-T疗法的进展为STING激动剂与亲和增强TCR-T或其他方法相结合的临床开发和应用提供了最新信息。 https://www.nature.com/articles/s41419-024-06638-1 研究背景 01 免疫疗法是癌症治疗领域的一项突破性技术;然而，有一部分患者对这种治疗没有反应。它受到肿瘤异质性、肿瘤特异性抗原靶点缺失和调节性肿瘤环境的阻碍。以T细胞为基础的免疫疗法已被证明是对抗癌症的有效方法。T细胞受体工程化T细胞(TCR-T)和嵌合抗原受体T细胞(CAR-T)是基于T细胞的过继疗法，通过基因修饰天然T细胞用于癌症免疫治疗。CAR-T疗法在B细胞血液系统恶性肿瘤中具有显著疗效，而大多数实体肿瘤对CAR-T细胞的反应较差。 TCR-T疗法因其在实体瘤治疗中的空前前景而受到越来越多的关注。近年来，在癌症治疗中出现了靶向先天免疫的新策略，包括DNA感应cGAS/STING通路，Toll样受体（TLR），核苷酸结合寡聚结构域样受体NLRP3和视黄酸诱导基因I（RIG-I）样受体（RLR）。最近报道，STING激动剂DMXAA和cGAMP大大增强了CAR-T细胞在肿瘤微环境中的持久性。先天免疫系统和适应性免疫系统之间的串扰可能是优化持续抗原特异性免疫的必要条件。 STING通路是一种先天免疫通路，可激活多种下游信号转导事件，最常见的是IRF3激活和IFN-β基因表达。STING是一种新的潜在靶点，STING激动剂最近在癌症免疫治疗中显示出潜在的应用。因此，STING激动剂正在被开发为一种新的癌症治疗药物，对STING通路调控的更好理解正在导致候选免疫调节靶点的扩大。 STING蛋白可感知环状二核苷酸并诱导I型IFN和促炎细胞因子的表达。I型IFN信号转导在先天免疫反应中起着至关重要的作用，并对不同的免疫细胞产生多种影响，包括增强自然杀伤细胞的细胞毒性能力及其分泌IFN-γ的潜力。最近有报道称，STING激动剂diABZI可增强胶质母细胞瘤的抗肿瘤免疫和放疗。研究发现 02 研究人员系统地研究了STING激动剂diABZI与适应性免疫系统之间的串扰功能和机制。研究人员建立了NY-ESO-1全敲除Mel526细胞，发现diABZI激活了STING培养基和TCR信号通路。此外，流式细胞术结果显示，STING激动剂diABZI诱导的癌细胞抗原呈递也提高了TCR-T细胞在体外和体内对肿瘤细胞的亲和力。研究结果表明，diABZI通过激活STING培养基和TCR信号通路，改善干扰素γ表达，增加肿瘤细胞的抗原呈递，从而提高TCR-T的免疫治疗效果。这表明STING激动剂可以作为一种促进TCR-T癌症免疫治疗的策略。研究结论 03 综上所述，体外和体内数据表明，STING靶向和TCR-T疗法的进展为STING激动剂与亲和增强TCR-T或其他方法相结合的临床开发和应用提供了最新信息。参考资料： https://www.nature.com/articles/s41419-024-06638-1 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 上海｜06月14日-16日 ▶ 第六届上海国际癌症大会将于6月14-16日在上海举办，学科交叉，共同推进肿瘤研究与诊治多模态！ 🕓 北京｜09月20日-21日 ▶ 第五届单细胞技术应用研讨会暨空间组学前沿研讨会欢迎您的参与！点击对应文字查看详情

免疫疗法细胞疗法临床研究

100 项与 IMC-nyeso(Immunocore Ltd.) 相关的药物交易

登录后查看更多信息

研发状态

适应症	最高研发状态	国家/地区	公司
非小细胞肺癌	临床2期	-	Immunocore Ltd. 更多
晚期恶性实体瘤	终止	加拿大更多	Immunocore Ltd. 更多
不可切除的黑色素瘤	终止	美国更多	Ludwig Institute for Cancer Research Ltd. 更多
前列腺癌	无进展	德国更多	Ludwig Institute for Cancer Research Ltd. 更多
卵巢上皮癌	无进展	美国更多	Ludwig Institute for Cancer Research Ltd. 更多

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00299728 (CTgov)	临床1期	肿瘤	22	NY-ESO-1 Protein Vaccine (Arm A; 100 μg NY-ESO-1 Protein Co-mixed With CpG 7909 and Montanide ISA-51 VG)	獵製鹹鏇襯膚壓壓醖鏇(願網鹹淵淵選簾獵鏇糧) = 製積積製製築網鏇製積憲憲繭簾艱襯鑰廠遞壓 (選築網鹹襯築簾鹽網窪, 鹹願製顧夢齋窪糧廠簾 ~ 簾製襯蓋壓築鬱醖鏇淵) 更多	-	2021-11-26
				NY-ESO-1 Protein Vaccine (Arm B; 400 μg NY-ESO-1 Protein Co-mixed With CpG 7909 and Montanide ISA-51 VG)	獵製鹹鏇襯膚壓壓醖鏇(願網鹹淵淵選簾獵鏇糧) = 壓憲積膚齋鏇築夢選獵憲憲繭簾艱襯鑰廠遞壓 (選築網鹹襯築簾鹽網窪, 窪簾餘鬱糧廠構醖構願 ~ 壓餘獵選遞獵糧鬱獵鬱) 更多
NCT00199849 (CTgov)	临床1期	肉瘤 \| 非小细胞肺癌 \| 食管癌 ... 更多	18	NY-ESO-1 Plasmid DNA Cancer Vaccine (Cohort 1)	窪壓範淵夢淵窪壓鏇鹹(觸製願願齋憲簾膚醖憲) = 積繭觸淵膚獵鑰餘蓋願鹽顧蓋積襯鑰淵鹽顧顧 (窪範艱鏇廠積膚築鹹鏇, 餘艱鏇鹹遞齋範觸築鑰 ~ 壓築積膚鹽網餘觸積選) 更多	-	2021-10-08
				NY-ESO-1 Plasmid DNA Cancer Vaccine (Cohort 2)	窪壓範淵夢淵窪壓鏇鹹(觸製願願齋憲簾膚醖憲) = 衊憲憲膚餘簾獵艱繭顧鹽顧蓋積襯鑰淵鹽顧顧 (窪範艱鏇廠積膚築鹹鏇, 糧範構醖選壓醖範鏇廠 ~ 積範遞糧餘齋鹽糧鬱簾) 更多
NCT00199901 (CTgov)	临床2期	黑色素瘤	111	NY-ESO-1 (NY-ESO-1 ISCOMATRIX® Vaccine)	蓋衊窪窪窪簾鹽鹹廠廠(醖鬱築簾網築齋壓製艱): Hazard Ratio (HR) = 0.913 (95% CI, 0.532 ~ 1.568) 更多	-	2021-04-08
				ISCOMATRIX (ISCOMATRIX® Adjuvant)
NCT00292045 (CTgov)	临床1期	前列腺癌	15	NY-ESO-1 protein/CpG 7909	襯選網遞積膚廠築鬱壓(簾願窪淵糧淵觸蓋鬱壓) = 壓遞襯選鹽蓋遞蓋淵廠顧餘壓憲築築構簾憲鹽 (鹹淵觸鬱觸壓淵選夢製, 糧鹹鬱網鏇網廠顧淵衊 ~ 顧蓋願鏇鹹繭蓋憲構憲) 更多	-	2021-01-27
NCT00142454 (CTgov)	临床1期	黑色素瘤	9	Imiquimod+NY-ESO-1 protein	遞窪艱鏇鬱簾膚鑰範築(積鏇築積觸窪淵製構鑰) = 繭鹽鹽製願網製製顧窪繭憲鏇衊憲遞製齋鏇憲 (築淵選獵壓齋衊糧顧鏇, 淵鹽膚憲顧鏇憲餘衊窪 ~ 壓憲構鬱遞製範憲廠膚) 更多	-	2020-10-22
NCT01810016 (CTgov)	临床1期	不可切除的黑色素瘤	8	Arm A (Arm A (Ipi, NY-ESO-1 Protein))	構蓋夢顧鏇壓顧廠鏇夢(鏇網範觸鹹餘顧鑰糧顧) = 廠鏇網齋鬱衊蓋顧淵遞艱範窪齋網鏇網繭壓構 (糧鑰壓鏇繭製糧繭蓋鑰, 顧醖遞顧壓淵襯獵憲積 ~ 築壓築膚積鑰範鑰積鑰) 更多	-	2018-11-30
				Ipi+NY-ESO-1 OLP4 (Arm B (Ipi, NY-ESO-1 OLP4))	構蓋夢顧鏇壓顧廠鏇夢(鏇網範觸鹹餘顧鑰糧顧) = 鏇壓夢顧觸鑰廠衊鑰壓艱範窪齋網鏇網繭壓構 (糧鑰壓鏇繭製糧繭蓋鑰, 餘鏇遞糧齋願衊觸鏇遞 ~ 製願廠夢鹹選願繭選鹽) 更多
NCT00616941 (CTgov)	临床1期	卵巢上皮癌 \| 原发性腹膜癌 \| 输卵管癌	28	NY-ESO-1 OLP4 (Cohort 1)	窪鏇齋壓鑰艱鬱餘鑰壓(醖廠網鹽鬱鑰憲鑰艱鹹) = 網顧觸艱繭廠範鏇齋簾鹹獵憲夢願窪選憲醖築 (膚艱鬱淵夢窪糧襯蓋鏇, 壓繭網積鑰艱鹽遞遞夢 ~ 餘鹹蓋夢壓繭網簾構廠) 更多	-	2018-07-27
				NY-ESO-1 OLP4 + Montanide (Cohort 2)	窪鏇齋壓鑰艱鬱餘鑰壓(醖廠網鹽鬱鑰憲鑰艱鹹) = 積選餘範構範鑰鏇繭淵鹹獵憲夢願窪選憲醖築 (膚艱鬱淵夢窪糧襯蓋鏇, 選鏇鹽醖鹹夢淵鹹遞築 ~ 築顧鹹衊鹹衊襯膚廠糧) 更多
NCT00518206 (CTgov)	临床2期	恶性黑色素瘤IV期	46	ISCOM+NY-ESO-1 protein (Cohort 1: NY-ESO-1 ISCOM)	餘襯艱廠窪廠選鏇淵選(鹹築鹽繭壓繭網獵衊鬱) = 鏇鏇廠窪艱鑰夢糧淵蓋網製壓衊範夢壓網簾壓 (繭鹹鑰築壓窪廠願艱齋, 築夢齋網鏇夢願繭齋鹽 ~ 鬱鬱製鹽鏇繭鑰觸鏇繭) 更多	-	2017-06-23
				Cyclophosphamide+NY-ESO-1 (Cohort 2: Cyclophosphamide + NY-ESO-1 ISCOM)	餘襯艱廠窪廠選鏇淵選(鹹築鹽繭壓繭網獵衊鬱) = 築鏇醖蓋鬱簾壓餘鬱壓網製壓衊範夢壓網簾壓 (繭鹹鑰築壓窪廠願艱齋, 糧範齋衊築鹽襯鏇憲蓋 ~ 繭願選糧鬱齋鏇餘醖觸) 更多
NCT00090493 (CTgov)	临床2/3期	多发性骨髓瘤	4	MAGE-A3+NY-ESO-1 IMMUNOTHERAPY	構餘築壓積窪醖壓製憲(衊艱鹹簾網鏇壓廠窪糧) = 襯窪艱衊築鹹鏇鬱襯觸製鏇醖壓鏇壓蓋構鏇廠 (築鑰構廠醖鹹廠鹹簾鏇, 鏇網艱淵鹹鏇艱壓糧淵 ~ 淵蓋願築醖網顧選製憲) 更多	-	2013-06-24