Cellular Medicine, Bioproduction, Thermo Fisher Scientific, 0309 Oslo, Norway.
Cell Biology, Thermo Fisher Scientific, Frederick, MD 21704, USA.
J Immunol Res. 2016;2016:5474602. doi: 10.1155/2016/5474602. Epub 2016 May 19.
The development of novel targeted therapies with acceptable safety profiles is critical to successful cancer outcomes with better survival rates. Immunotherapy offers promising opportunities with the potential to induce sustained remissions in patients with refractory disease. Recent dramatic clinical responses in trials with gene modified T cells expressing chimeric antigen receptors (CARs) in B-cell malignancies have generated great enthusiasm. This therapy might pave the way for a potential paradigm shift in the way we treat refractory or relapsed cancers. CARs are genetically engineered receptors that combine the specific binding domains from a tumor targeting antibody with T cell signaling domains to allow specifically targeted antibody redirected T cell activation. Despite current successes in hematological cancers, we are only in the beginning of exploring the powerful potential of CAR redirected T cells in the control and elimination of resistant, metastatic, or recurrent nonhematological cancers. This review discusses the application of the CAR T cell therapy, its challenges, and strategies for successful clinical and commercial translation.
开发具有可接受安全性特征的新型靶向疗法对于提高癌症患者的生存率和获得成功的治疗结果至关重要。免疫疗法为患有难治性疾病的患者带来了有希望的机会,有可能诱导持续缓解。在 B 细胞恶性肿瘤中表达嵌合抗原受体 (CAR) 的基因修饰 T 细胞的临床试验中,最近取得了显著的临床反应,这引起了极大的关注。这种治疗方法可能为我们治疗难治性或复发性癌症的方式带来潜在的范式转变。CAR 是经过基因工程改造的受体,它将肿瘤靶向抗体的特异性结合结构域与 T 细胞信号结构域结合在一起,从而允许特异性靶向抗体重新定向 T 细胞激活。尽管在血液癌症方面取得了当前的成功,但我们才刚刚开始探索 CAR 重新定向 T 细胞在控制和消除耐药、转移性或复发性非血液癌症方面的强大潜力。本文综述了 CAR T 细胞疗法的应用、挑战以及成功进行临床和商业化转化的策略。