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我们的TCR-T技术是利用我们独特的人工抗原提成细胞技术制备肿瘤特异性的CTLs, 然后从分离得到的单个抗原肽-Tetramer阳性的CTL细胞中测定其基因顺序。运用DNA重组技术将克隆得到的高亲和性的TCRα和β链基因片段插入到逆转录病毒或慢病毒等基因转导载体中。通过不同基因转导技术将TCR基因转导至外周血T细胞,使其表达抗原特异性TCR,成为能够特异性识别肿瘤抗原的CTL,体外扩增并回输病人,达到体内杀死肿瘤细胞的作用。我们目前选择的靶分子是NY-ESO-1,全称New York esophageal squamous cell carcinoma 1,是肿瘤-**抗原(cancer-testis antigens,  CTA)家族重要成员之一。NY-ESO-1具有诱导体液免疫应答的能力, 也具有激活CD4 +和CD8 + T淋巴细胞的能力, 是到目前为止被发现的免疫原性*强大的肿瘤特异性抗原。NY-ESO-1在多种肿瘤细胞中都有表达,包括黑色素瘤、食道癌、膀胱癌、肺癌等。但 NY-ESO-1 在除**组织以外的正常组织不表达,**组织不表达 MHC  I 类及 II 类分子,所以不会被 T 细胞识别杀伤。正是由于这一特征,NY-ESO-1 成为了肿瘤免疫治疗研究的热点。技术特点l  保持TCR和共刺激因子相互作用的天然结构,既保留信号激活的强度,又保证了强度的控制,因而更强,更有效地激活重新编程的T细胞,也具有一定的安全性;l  高效的特异TCR克隆选择系统;l  特异TCR在CTL细胞表面的高密度表达,提高了对肿瘤特异识别和杀伤作用。TCR-T Technology    Our TCR-T technique is featured by using the patented artificial antigen presentation system to prepare tumor specific CTL cells. The sequences coding for TCRα and βsubunits are decoded and cloned from antigen peptide-Tetramer positive cells. The TCRα and β gene will then be inserted into retroviruses or lentiviruses derived vectors and transduced into peripheral blood derived T cells for high expression of antigen-specific TCR to become tumor-specific CTL clone (TCR-T) and to obtain potent tumor cell killing activity.    Currently, we are focused on target molecule NY-ESO-1 (New York esophageal squamous cell carcinoma 1), an important member of cancer-testis antigens (CTA) family. NY-ESO-1 can induce humoral immune response and activate CD4+ and CD8+ T-lymphocytes. NY-ESO-1 is widely expressed in a variety of tumor cells such as melanoma, esophageal cancer, bladder cancer, lung cancer and exhibits, thus far, strongest immunogenicity among all tumor-specific antigens. NY-ESO-1 has not been detected in normal tissues except in testicular tissue. Testis cells do not express MHC-I and MHC-II molecules, thereby escaping T cell attack via NY-ESO-1 target. This unique property makes NY-ESO-1 a hotspot in tumor immunotherapy research.Technical features1.    Maintaining the natural structure of TCR for proper interaction with cofactors, not only        maintains the strength of activation signal, but also ensures the control of activation        strength, and thus manifests safety2.    Efficient and specific system of TCR cloning and screening3.    Higher expression of specific TCR enables CTLto recognizie and kill tumor cells with more        efficiency 

嵌合抗原受体T细胞(CAR-T细胞)是在体外构建一个嵌合基因,包括识别肿瘤抗原的单链抗体可变区的基因片段和T细胞激活辅助因子的基因片段,然后通过转导的方法转染患者的T细胞,即“重编码”患者的T细胞,使其表达嵌合抗原受体(CAR)。经体外培养生成大量肿瘤特异性的CAR-T细胞,回输到患者体内,达到有效识别和杀伤肿瘤细胞的目的。技术特点l  靶点不受MHC的限制;l  识别靶分子的亲和力强,有效捕捉癌细胞;l  可设计成多靶点的CAR基因,减少或者消除细胞因子释放症的副作用;l  具有免疫记忆功能。CAR-T Technology     Chimeric antigen receptors T cells (CAR-T) designates the technology that engineers receptors (usually single chain monoclonal antibody plus the sequence of T cell costimulatory domains) and expresses them on  T cells. Thus constructed CAR-T cells specifically recognize and kill tumor cells, as demonstrated in vitro and in vivo. Technical features1.    Targets are not restrained by MHC, broad-spectrum indications2.    Strong affinity to the target molecules on cancer cells, efficient killing of cancer cells in        culture or in circulating system;3.    can be designed to multiple target points and more accurate, to reduce side effects of        cytokine release 4.    With immune memory function

CD8 T细胞治疗技术是从癌症患者的血液中分离出CD8 T细胞,在体外经独特的负载肿瘤抗原肽的人工抗原提呈细胞(APC)高效诱导激活分化,成为具有特异靶向性杀伤功能的CD8毒性T细胞(CTL),经体外扩增后回输到人体以杀灭体内肿瘤细胞,以及调节和增强人体自身的抗肿瘤的免疫功能。人工抗原提呈细胞能**限度负载抗原肽,有效刺激CD8 T细胞成为肿瘤特异性的CD8毒性细胞,发挥杀伤肿瘤细胞的功能。临床试验数据已证明经人工抗原提成细胞诱导的特异性CD8 T细胞治疗的安全性和有效性(美国已完成二期临床试验,NCT00512889)。技术特点1.    自主知识产权,已授权(**号:201310439121.1);2.    用独特的方法发现和确定黑色素瘤和肺癌抗原肽;3.    特异高效的人工抗原提呈细胞株;4.    独特的工艺流程制备肿瘤特异性的T细胞。Tumor specific CD8 T cell therapy Tumor specific CD8 T cell therapy technology includes: 1) separating CD8 T cells from the blood of cancer patients; 2) Inducing and activating subgroup(s) of CD8 T cells by Antigen Presenting Cells (APC) loaded with tumor antigen peptide(s); 3) expanding CD8 toxic T cells (CTL) ; 4) Harvesting CTLs, and infusing back to the donor to kill the tumor cells. Clinical trial data have demonstrated the effectiveness of this technology (clinical trail registration: NCT00512889)。. Highlights in our technology 1.    Patented technology  involved (patent No:201310439121.1);;2.    With a unique method to identify tumor antigen peptides; 3.    Employing an artificial Antigen Presenting Cell lines, which allows for higher density loading       of the tumor antigen peptides ; 4.    Unique protocol for preparing tumor targeting T cells

人羊膜上皮细胞具有干细胞的特性和多分化潜能, 并且具有一些优良特性。首先,羊膜上皮干细胞分泌丰富的生长因子,尤其是多种神经生长因子和神经递质,赋予其在神经功能调整和神经损伤修复上的特殊功效;其次,羊膜上皮干细胞来自于胚胎期,经历的细胞分裂代数比较少,突变积累程度相对低,因此安全性高; 还有,羊膜上皮干细胞端粒酶水平很低,分裂代数有限(5-8代),临床应用上无致瘤风险。功能Ø  通过分泌的细胞因子,激活患者自身的修复反应,促进损伤组织的血管形成、神经再生等过程;Ø  通过分泌的细胞因子,作用于机体的各个部分,增强机体的整体活力,延缓衰老,改善容颜;Ø  通过分泌的免疫抑制因子,控制和调节机体的免疫平衡,降低过度的炎症反应,减少损伤部位细胞的死亡数量。产品/技术优点制备技术成熟,细胞制剂质量好,分泌细胞因子丰富,功能强,安全性高。Human amniotic epithelial cells (hAECs)hAECs are pluripotent stem cells. hAECs secrete abundant nerve growth factors and neurotransmitters, in addition to general growth factors, to make the cells especially useful in neural function adjustment and nerve injury repairing. Because of at the stage of  embryo development, the cells have experienced relatively fewer cell divisions and accumulated a low degree of somatic mutation, implying low risk in application. Of note, hAECs possess very low telomerase activity, therefore, have limited division cycles (5-8 generations), an indication of free tumorogenic risk in clinical application. Features and functions1.    A rich mixture of cell growth factors from hASCs will activate damage fixing mechanisms in recipients, through promoting the vascular formation, nerve regeneration and other processes in injured tissues; 2.    A rich types of cell growth factors from hASCs will enhance body’s vitality, increase anti-aging capacity and improve facial appearance; 3.    Immunosuppressive factors from hASCs will play roles in controlling and regulating immune balance to inhibit excessive inflammation and thereby to reduce the cell mortality in the inflammatory sites; Highlights in our technology/products1.    Well tuned preparing technique;2.    Therefore, sustained and good quality of cell preparation.

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