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第四代CARs技术:TRUCKs

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发表于 2016-1-4 21:56:57 | 显示全部楼层 |阅读模式
TRUCKs: the fourth generation of CARs.
INTRODUCTION:
Adoptive cell therapy of malignant diseases takes advantage of the cellular immune system to recognize and destroy cancer cells. This is impressively demonstrated by redirecting T cells with a chimeric antigen receptor (CAR) towards CD19, inducing complete and lasting remission of leukemia in more than two-thirds of patients in early phase trials.
AREAS COVERED:
We outline how the CAR strategy is highly specific in redirecting T cells towards pre-defined target cells, however, reaches its limits when targeting solid tumors with a tremendous phenotypic heterogeneity. After initial tumor reduction by CAR T cells, antigen-negative cancer cells not recognized by CAR may give rise to tumor relapse. The situation may be overcome by CAR-mediated activation of T cells in the tumor, releasing inducible IL-12 which augments T-cell activation and attracts and activates innate immune cells to eliminate antigen-negative cancer cells in the targeted lesion.
EXPERT OPINION:
CAR T cells with a transgenic 'payload', so-called TRUCK T cells or the 'fourth-generation' CAR T cells, are worthwhile to explore to shape the tumor environment by the inducible release of transgenic immune modifiers. Such TRUCK T cells are moreover envisioned to be applied in fields beyond cancer therapy including the therapy of virus infections, auto-immune diseases or metabolic disorders.
KEYWORDS:
IL-12; T cell; adoptive cell therapy; chimeric antigen receptor; inducible cytokine; innate immunity
第四代CARs技术:TRUCKs
介绍:
肿瘤疾病的过继细胞治疗充分发挥了细胞免疫系统来识别和破坏肿瘤细胞。这个技术被靶向CD19的嵌合抗原受体修饰的T细胞技术充分的证明了,在早期的临床试验中,超过了2/3的白血病病人得到了完全和持续性的缓解。
包含的内容:
我们描述了CAR是如何高效的特异性的诱导T细胞对抗靶细胞的策略。然而,当对抗实体肿瘤时会有巨大的表型的不均一性,从而CAR-T技术受到限制。通过CAR-T细胞的处理,初始的肿瘤减少之后,抗原阴性的肿瘤细胞并不能被CAR识别,从而导致了肿瘤的逃逸。这种情况可能被CAR介导的肿瘤中的T细胞活化而克服,通过释放IL-12,能够促使T细胞活化和吸引,使得原始的免疫细胞消除抗原阴性癌细胞。
专家观点:
伴有转基因的“有效载荷”的CAR-T细胞,被称为TRUCK-T细胞,或者是第四代的CAR-T细胞技术,这是是值得探索的,通过转基因免疫调节剂的诱导释放来塑造肿瘤微环境。这种TRUCK-T 细胞技术在癌症治疗之外,包括治疗病毒感染,自体免疫疾病或代谢性疾病等疾病的治疗中,都是可以应用的。
关键词:
IL-12T细胞;过继性细胞治疗;嵌合抗原受体诱导的细胞因子;先天免疫;
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