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TCR-T 细胞技术平台
 

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最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TCRCTL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 features

1.    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 safety

2.    Efficient and specific system of TCR cloning and screening

3.    Higher expression of specific TCR enables CTLto recognizie and kill tumor cells with more

       efficiency


 

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