年终盘点：2018年细胞治疗重要研究盘点(2)

2018-12-25 22:45:01

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2018年4月，鉴于干性AMD（年龄相关性黄斑变性）产生的原因在于视网膜色素上皮细胞（retinal pigment epithelium, RPE）的退化和死亡，Amir H. Kashani等人在一项1/2a期临床试验中，通过让人类胚胎干细胞分化而成的RPE细胞（human embryonic stem cell-derived RPE, hESC-RPE）在人工合成的骨架上生长成为一个单细胞层，从而构建出一种RPE复合种植体，随后四名晚期干性AMD患者接受了移植手术，结果表明，这种移植体不但能够阻止病情的进一步恶化，而且给有些患者的视力带来了显著改善[23]。

2018年3月，鉴于当T细胞在对抗感染时，T细胞表面上的一个称为41BB的共刺激因子会被是激活，但是在肿瘤内部环境中，它失活了，Greg M. Delgoffe等人在实验室培养的小鼠T细胞中，发现一个蛋白抗体可以激活41BB，导致T细胞的线粒体数量增加，且互相融合[24]。他们还发现在对免疫检查点阻断疗法和过继性T细胞疗法响应率都很低的小鼠黑素瘤模型中，当这种蛋白抗体与免疫检查点阻断疗法或过继性T细胞疗法联合使用中，联合使用的疗效优于两种疗法的单纯相加。 [转载出处：www.ii77.com]

年终盘点：2018年细胞治疗重要研究盘点
图13. 图片来自Journal of Experimental Medicine, doi:10.1084/jem.20171068。

其实，科学家们针对细胞治疗领域的研究不胜枚举，以上罗列的仅是其中的一小部分。当然，其中的一些涉及细胞治疗的研究仅局限在细胞模型和动物模型上，或者虽然已开展人体临床试验，但是仍然停留在I期或II期临床试验阶段，参与临床试验的患者人数仍然偏少，仍需通过招募更多的患者人数来开展III期临床试验。因此，最终能否得到各国监管机构的批准，仍是未知数。去年，美国FDA批准了两种CAR - T细胞产品上市——诺华公司(Novartis)的CAR-T细胞免疫疗法Kymriah（tisagenlecleucel，CTL-019）和Kite制药公司的CAR-T细胞免疫疗法Yescarta（axicabtagene ciloleucel），分别用于治疗儿童和年轻人B细胞急性淋巴细胞白血病（ALL）和成人复发或难治性大B细胞淋巴瘤患者。然而，CAR-T细胞免疫疗法尽管在治疗血液肿瘤中有巨大的希望，但是同时也存在较大的副作用。CAR-T细胞免疫疗法带来一个巨大的临床风险就是细胞因子风暴。当CAR-T细胞快速杀死癌细胞时，产生的大量细胞因子会对宿主其他组织器官发起惊人的攻击，导致高烧、低压、休克甚至死亡。此外，血液肿瘤仅是癌症中的一小部分。作为癌症中的大头，实体瘤远比血液肿瘤复杂得多。尽管初步研究已表明CAR-T细胞免疫疗法在实体瘤方面具有不错的安全性和有效性，但是接受治疗的患者也会出现败血症、气短和白细胞水平升高等副作用，对实体瘤的治疗似乎并没有想象中的那么乐观。不过，在未来，随着科学家们不断取得新的突破，诸如CAR - T细胞疗法之类的细胞疗法有望为更多患者带来福音。

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