Primary brain malignant tumor has become the first lethal tumor in children and young adults, and the treatment is limited, and the prognosis of patients is poor. According to the classification of the World Health Organization, glioblastoma is divided into grade II, III and IV gliomas; The higher the degree of malignancy, the worse the clinical outcome. Among them, the most malignant, most lethal, and most common types of tumors include supratentorial glioblastoma, diffuse endopontine glioma (DIPG), medulloblastoma, and ependymoma. Its high malignancy is mainly manifested in three aspects: extremely rapid growth and obvious invasion; The operation is not easy to remove all; The tumor has a tendency of recurrence and disseminated implantation. It can occur with children and adults of all ages. At present, surgery combined with chemoradiotherapy is the main treatment, but the therapeutic effect is not good. Studies have shown that glioblastoma, as the most common primary brain malignant tumor in adults, after standard surgery, radiotherapy and chemotherapy, the median survival time is less than 15 months, and the overall five-year survival rate is only 5.4%. Even after receiving new and expensive Tumor-treating fields, the median survival time is less than 21 months. The median survival time of DIPG patients is generally less than 1 year, and the 5-year survival rate is less than 5%. The average 5-year survival rate of medulloblastoma and anaplastic ependymoma is 40%
60%. Innovative treatments are urgently needed. Immunotherapy based on Vγ9Vδ2 T cells has become a promising research direction in recent years. Its unique phosphine antigen recognition does not depend on major histocompatibility complex (MHC), easy to allograft and other advantages. Making it one of the most promising cell therapies. Brain glioma has abnormal cholesterol metabolism and phosphine antigen accumulation, which is easily sensed by Vγ9Vδ2 T cells. Therefore, the clinical exploration of Vγ9Vδ2 T cells for glioma is of great significance to both the scientific and clinical communities.

开始日期2024-04-30

申办/合作机构

北京天坛医院

100 项与 Vγ9Vδ2 T cell(Beijing Tiantan Hospital) 相关的临床结果

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100 项与 Vγ9Vδ2 T cell(Beijing Tiantan Hospital) 相关的转化医学

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100 项与 Vγ9Vδ2 T cell(Beijing Tiantan Hospital) 相关的专利（医药）

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项与 Vγ9Vδ2 T cell(Beijing Tiantan Hospital) 相关的文献（医药）

2024-12-01·Immuno-Oncology and Technology

An organotypic human melanoma-in-skin model as an in vitro tool for testing Vγ9Vδ2-T cell-based immunotherapy

Article

作者: van der Vliet, Hans J. ; Gibbs, S. ; Veth, M ; Spiekstra, S W ; Spiekstra, Sander W. ; Michielon, Elisabetta ; Waaijman, T. ; King, Lisa A. ; de Gruijl, Tanja D. ; Waaijman, Taco ; King, L.A. ; de Gruijl, T D ; Gibbs, Susan ; King, L A ; de Gruijl, T.D. ; Michielon, E. ; Veth, M. ; Waaijman, T ; Michielon, E ; van der Vliet, H.J. ; van der Vliet, H J ; Veth, Myrthe ; Spiekstra, S.W. ; Gibbs, S

BackgroundDespite considerable advancements in cancer immunotherapy, advanced melanoma still presents a substantial clinical challenge. In an effort to explore treatment options, we examined the immunotherapeutic potential of effector Vγ9Vδ2-T cells in vitro in a three-dimensional (3D) human organotypic melanoma-in-skin (Mel-RhS) model.Materials and methodsVγ9Vδ2-T cells were introduced into Mel-RhS via intradermal injection and cultured within the tissue microenvironment for up to 3 days.ResultsVγ9Vδ2-T cells remained viable for up to 3 days and were in close proximity to or within tumor nests. Upon Mel-RhS dissociation, a fraction was shown to be decorated by melanoma-associated chondroitin sulfate proteoglycan (MCSP), demonstrating their ability to actively navigate the tumor microenvironment and trogocytose cancer cells. Investigation into the apparent trogocytosis revealed an enhanced activated state of MCSP-decorated Vγ9Vδ2-T cells, evidenced by increased expression levels of 4-1BB, NKp44, programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1), compared with their MCSP^- counterpart. These findings suggest that Vγ9Vδ2-T cells, upon successfully contacting melanoma cells, actively recognize and acquire MCSP from these malignant cells. Evidence of actual tumor cell elimination, although not significant, was only obtained after preincubation of Mel-RhS with pamidronate, a phosphoantigen-inducing agent, indicating the need for additional T cell receptor-mediated signaling for Vγ9Vδ2-T cells to reach their full oncolytic potential.ConclusionsThis study highlights the viability and persistence of Vγ9Vδ2-T cells within the 3D microenvironment, their migratory and antitumor functionality, and the suitability of the model for testing T cell-based therapies, contributing both to the understanding of Vγ9Vδ2-T cell biology and their application in cancer immunotherapy.

项与 Vγ9Vδ2 T cell(Beijing Tiantan Hospital) 相关的新闻（医药）

2024-09-04

·今日头条

港大医学院引进亚洲第一个无痛、无创抗癌的“组织碎化术”！

2024年08月29日，据“有线新闻”报道，李嘉诚基金会投放4680万元，向港大医学院捐赠亚洲首部突破性创新医疗仪器——Histotripsy系统，利用全球顶尖的“组织碎化术”无创碎化肿瘤，为肝癌患者提供治疗，组织碎化术适用于体积＜5cm3的肿瘤，手术不会伤及健康组织，术后最快1~2天即可出院。港大医学院也宣布将开展亚洲首个基于组织碎化术的临床研究！第一位患者预计将于本星期接受该治疗，让我们拭目以待其效果，同时也希望内地可以尽快引进，让更多的癌症患者获益！ ▲图源“stem cells journals”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除一、获FDA批准的“组织碎化术”：开启癌症治疗新篇章组织碎化技术是由美国研发的一款非侵入性、非电离、非热消融的新型抗癌技术，利用高强度超声波选择性地破坏癌细胞，而不会损害周围的健康组织。于2023年10月，获得美国食品药品管理局（FDA）批准，用于原发性和转移性肝肿瘤的治疗。临床数据显示，接受治疗的患者术后恢复良好，目标肿瘤未出现局部复发，也未见治疗相关严重并发症，说明这项技术安全有效。而且与传统消融、放疗或手术相比，组织碎化技术无需切口、辐射或侵入性操作。 Histotripsy系统由机械臂、水床、超声波发射器等组成，治疗时医生会使用超声成像技术来定位肿瘤，机器会精确地产生聚焦声波，瞄准癌细胞，在肿瘤内形成微气泡。这些气泡迅速膨胀和收缩，会产生冲击波破坏和液化目标肿瘤细胞，使其变成无细胞碎片，这些残留的碎片会被免疫系统清理。此外，组织碎裂术还可打破癌细胞壁的“外衣”，使肿瘤抗原暴露，让免疫系统可以识别这些抗原，并利用它们对其他癌细胞进行有针对性的攻击。 ▲图源“stem cells journals”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除虽然目前仅获批用于肝癌的治疗，但从理论上说，如果我们用超声波看到肿瘤，未来有一天，或许我们就能利用组织碎化技术进行治疗。欣慰的是，目前研究人员正在研究将该技术用于胰腺癌、肾脏肿瘤等多项实体瘤的治疗。 ▲图源“EMJ”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除注： ①图A：治疗用超声换能器+诊断用超声换能器（蓝色箭头）； ②图B：气泡云在B超上呈现高回声，在规划过程中，选择治疗区（红色圆圈），并将气泡云与十字线（红色十字线）对齐，红圈内的治疗组织呈现低回声。二、多款抗癌新药、新技术联手抗癌，助患者获得更长生存、更高生活质量虽然组织碎化技术已获得FDA批准，且在香港开展了临床研究，但距离在我国正式获批可能还有一段路要走。不过值得欣慰的是，近十余年来肝癌的治疗取得了长足的进展，有多款抗癌新药、新技术相继涌现，为肝癌患者带来了“希望的曙光”！我们在翘首企盼该技术能尽快引进内地的同时，也为大家简单盘点一下肝癌的新药、新技术，以供癌友们参考，增加与癌抗争的决心！（一）十余款获批上市的肝癌靶向药/免疫治疗药物截至2024年1月，获美国食品药品监督管理局（FDA）和中国药品监督管理局（NMPA）批准的肝癌靶向/免疫治疗药物共计13款。而且众多抗癌新药，都在中国陆续开展临床试验，这也意味着中国患者有免费获得美国最新抗癌药物治疗的机会。患者可将治疗经历、近期病理检查、影像学检查资料，提交至全球肿瘤医生网医学部，了解详细的入排标准或进行初步评估。（二）GPC3 CAR-T细胞：超90%的肝细胞癌患者肿瘤病灶缩小！ GPC3是肝细胞癌治疗中，非常具有潜力的一个靶点，其在肝癌细胞表面过度表达，但在正常细胞中低表达。针对该靶点研发的一款GPC3 CAR-T细胞疗法，在2024年ASCO大会上公布了I期临床研究（NCT05155189）的惊艳结果。本次共入组24例晚期肝细胞癌患者，既往接受过中位3.5种全身治疗，83%的患者伴肝外转移。入组后，入组接受淋巴细胞清除+C-CAR031回输治疗后，结果显示： 1、客观缓解率（ORR）：所有剂量水平患者的ORR达到 56.5% ，其中7位接受C-CAR031最高剂量治疗的患者，客观缓解率（ORR）更是高达 75.0% 。 2、疾病控制率（DCR）：所有剂量水平患者的疾病控制率高达 91.3% ！这也意味着，超九成的患者在接受C-CAR031治疗后，肝内和肝外肿瘤病灶出现缩小表现，肿瘤中位缩小率达到 42.2% 。 ▲图源“ApexOnco”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除（三）SCG101 TCR-T细胞，一箭双雕抗癌及抗乙肝病毒 SCG101是一种乙肝抗原特异性的TCR-T细胞疗法，其新药IND于2022年3月获中国国家药品监督管理局（NMPA）批准，该药兼具抗癌和抗病毒的双重功效，可通常清除HBV-HCC肿瘤细胞、HBV-DNA整合的癌前病变细胞、HBV感染细胞。 2023年国际细胞与基因治疗大会（ISCT）上，公布了其突破性的临床数据，一位乙肝病毒（HBV）相关肝细胞癌患者，在接受单剂SCG101治疗后，获得部分缓解（PR），不仅肿瘤病灶缩小，且HBV感染也得到缓解。 1、肿瘤病灶缩小：SCG101治疗后第28天，肿瘤靶病灶比基线时缩小 66% ；治疗第4个月时，治疗病灶进一步缩小至 74.5% ；同时另一处病灶完全消失。且该患者肿瘤未进展时间已超过6.9个月。 ▼该患者在SCG101治疗前后的影像学变化 ▲图源“CISION”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 2、 HBV感染缓解：该患者在回输SCG101后，肝脏免疫组化结果显示，乙肝表面抗原阳性肝细胞实现100%清除。与此同时， HBsAg（HBV血清学标志）水平也迅速下降，从 557.96IU/mL （治疗前），下降至 1.3 IU/mL （回输第7天）、 0.08 IU/mL （回输SCG101第28天）。 ▼该患者在SCG101治疗前后的HBsAg水平变化 ▲图源“CISION”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除（四）γδT助晚期肝癌患者，生存期延长近3倍！ γδ T细胞无需树突状细胞（DC）的参与即可直接杀死靶细胞，并在抗肿瘤和抗感染免疫中发挥双重功能。一项关于“Vγ9Vδ2细胞（γδ T细胞中的主要亚群）治疗晚期癌症的临床研究”，共入组18例患者，其中8例为肝癌患者，另10例为肺癌患者。治疗后结果显示，肝癌组患者在接受Vγ9Vδ2细胞治疗后，中位生存时间大幅延长，为 23.1个月（γδ T细胞治疗组） vs 8.1个月（对照组），与对照组相比，Vγ9Vδ2细胞助患者生存期延长近3倍。值得一提的是，在2020年6月的随访中，3例患者仍存活，目前生存期长达30~35个月（详见下图）。 ▲图源“Cell Mol Immunol”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除（五）肝癌粪便微生物群移植后，肿瘤显著缩小47.7%！除了抗癌新药、免疫细胞治疗外，粪便微生物群移植（FMT）在肝癌治疗中，也取得了不俗的效果。在一项“应用粪便微生物群移植，治疗晚期难治性胃肠道肿瘤”的临床研究（NCT04264975）中，1位对纳武单抗耐药的转移性肝细胞癌（HCC）患者（患者R7），在接受粪便微生物群移植（FMT）+持续免疫治疗后，肿瘤病灶显著缩小近50%，并最终获得部分缓解（PR）。该患者第2次粪便微生物群移植8周后，肿瘤标志物 [PIVKA-II（拮抗剂II诱导蛋白）、血清甲胎蛋白（AFP）] 显著下降；且肿瘤显著缩小了30.5% ，之后又进一步缩小至4 7.7% ，并最终获得部分缓解（PR）（详见下图）。 ▲图源“Cell Host Microbe”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除注：在第二次FMT8周后，肿瘤缩小，并实现PR（下方红色星号）。三、小编寄语在过去十年间，肝癌治疗已取得了长足的进展，尤其是随着CAR-T、TCR-T、γδ T细胞、癌症疫苗、益生菌、粪便微生物群移植等新型疗法，以及多款抗癌新药的相继的出现，逆转了晚期肝癌患者的生存期。近期港大又引进了美国这款不久前才获批上市的新型组织碎化术，为肝癌患者乃至实体瘤患者提供了新的希望！全球肿瘤医生网小编也期望未来会有更多的抗癌新兴疗法上市，从而实现巩固治疗效果、延长生存期、预防复发、提高生存质量等目的，让越来越多的癌症患者获益！四、参考资料 [1]Xu Z,et al.Vlaisavljevich E, Lee FT Jr. Histotripsy: the first noninvasive, non-ionizing, non-thermal ablation technique based on ultrasound. Int J Hyperthermia. 2021;38(1):561-575. doi: 10.1080/02656736.2021.1905189. PMID: 33827375; PMCID: PMC9404673. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404673/ [2]Kisting M A,et al.Imaging for targeting, monitoring, and assessment after histotripsy: a non-invasive, non-thermal therapy for cancer[J]. blood vessels, 2023, 10: 15-21. https://www.emjreviews.com/radiology/article/imaging-for-targeting-monitoring-and-assessment-after-histotripsy-a-non-invasive-non-thermal-therapy-for-cancer/ [3]Xu Y,et al.Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer. Cell Mol Immunol. 2021 Feb;18(2):427-439. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027668/ [4]https://www.oncologypipeline.com/apexonco/asco-2024-astrazenecas-gpc3-secret-sauce [5]https://www.i-cable.com/%E6%96%B0%E8%81%9E%E8%B3%87%E8%A8%8A/264261/%E6%B8%AF%E5%A4%A7%E7%8D%B2%E6%9D%8E%E5%98%89%E8%AA%A0%E5%9F%BA%E9%87%91%E6%8D%90%E8%B4%88%E4%BA%9E%E6%B4%B2%E9%A6%96%E9%83%A8%E7%84%A1%E5%89%B5%E7%A2%8E%E5%8C%96%E8%85%AB%E7%98%A4%E5%84%80%E5%99%A8 本文为全球肿瘤医生网原创，未经授权严禁转载

突破性疗法临床研究

2023-12-08

·Science Daily

How immune cells recognize their enemies

In order for immune cells to do their job, they need to know against whom they should direct their attack. Research teams a have identified new details in this process. As complicated as their name is, they are important for the human organism in the fight against pathogens and cancer: Vγ9Vδ2 T cells are part of the immune system and, as a subgroup of white blood cells, fight tumor cells and cells infected with pathogens. They recognize their potential victims by their altered cell metabolism. Research teams from the University of Würzburg and the University Hospital of Würzburg, together with groups in Hamburg, Freiburg, Great Britain and the USA, have now gained new insights into how these cells manage to look inside the cell. Thomas Herrmann, Professor of Immunogenetics at the Institute of Virology and Immunobiology and his colleague Dr. Mohindar Karunakaran at Julius-Maximilians-Universität Würzburg (JMU), were responsible for the study published in the journal Nature Communications. Crucial for the Control of Infections and Tumors "Around one to five percent of lymphocytes, a subgroup of white blood cells in the human body, are so-called Vγ9Vδ2 T cells. However, these multiply massively under certain circumstances," says Thomas Herrmann, explaining the background to the research project. "Certain circumstances" in this case means that the T cells encounter so-called phosphoantigens, metabolic products of pathogens, which can also accumulate spontaneously in tumor cells or after drug-based cancer therapy. "Vγ9Vδ2 T cells are therefore crucial for the control of infections and tumors," explains Herrmann. Receptors Give the Signal to Kill As the scientists discovered, phosphoantigens bind to a special group of molecules inside the cell, the so-called BTN3A1 molecules, with which they then form molecular complexes. "These complexes are recognized by receptors on the surface of the Vγ9Vδ2 T cells, which gives the cell the signal to kill," says the immunogeneticist. However, it turned out that relatives of the BTN3A1 molecules that do not bind phosphoantigens are also required to trigger these signals. Which areas of the molecules involved react with each other and which areas are not necessary for this: The research groups have now identified further details on this. "These findings can improve the clinical use of Vγ9Vδ2 T cells in the fight against tumors," explains Herrmann. On this basis, it is conceivable, for example, to develop drugs that strengthen this interaction. However, further analyses of the interaction between the BTN molecules and the receptors of the Vγ9Vδ2 T cells are still required. Some BTN Molecules Prevent Infections However, the BTN molecules are also interesting from another point of view: "Some forms of the BTN3 molecules prevent human cells from becoming infected with the bird flu virus, for example," says Herrmann. And the BTN3A1 molecule suppresses the fight against tumors by so-called conventional T lymphocytes. In future studies, the scientists therefore now want to investigate whether these different functions are mediated by the same areas of the BTN molecules and whether certain properties of these molecules can be specifically enhanced or suppressed.

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适应症	最高研发状态	国家/地区	公司	日期
弥漫内生性脑桥神经胶质瘤	临床1期	中国	北京天坛医院	2024-04-30
多形性胶质母细胞瘤	临床1期	中国	北京天坛医院	2024-04-30
脑恶性胶质瘤	临床1期	中国	北京天坛医院	2024-04-30
髓母细胞瘤	临床1期	中国	北京天坛医院	2024-04-30