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cart细胞治疗及其副作用

2021-11-09
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你的免疫系统通过跟踪你体内正常存在的所有物质来工作。任何免疫系统无法识别的新物质都会发出警报,导致免疫系统攻击它。


嵌合抗原受体(CAR)T细胞疗法是一种让免疫细胞T细胞(一种白血球)在实验室中进行改变,从而发现并摧毁癌细胞的方法。CAR T细胞疗法有时也被称为一种基于细胞的基因疗法,因为它涉及改变T细胞内的基因以帮助它们攻击癌症。


这种类型的治疗对治疗某些类型的癌症非常有帮助,即使其他治疗不再有效。


CAR T细胞疗法的工作原理


免疫受体和外来抗原


免疫系统通过在细胞表面发现称为抗原的蛋白质来识别体内的异物。被称为T细胞的免疫细胞有自己的蛋白质,称为受体,它附着在外来抗原上,并帮助触发免疫系统的其他部分破坏外来物质。


抗原和免疫受体之间的关系就像一把锁和一把钥匙。正如锁只能用正确的钥匙打开一样,每个外来抗原都有一个独特的免疫受体,能够与之结合。


癌细胞也有抗原,但如果你的免疫细胞没有正确的受体,它们就不能附着抗原并帮助破坏癌细胞。


嵌合抗原受体(CARs)


在CAR T细胞疗法中,T细胞取自患者的血液,并在实验室通过添加人造受体(称为嵌合抗原受体或CAR)的基因进行改变。这有助于他们更好地识别特定的癌细胞抗原。然后将CAR T细胞返回给患者。


由于不同的癌症有不同的抗原,每辆车都是针对特定的癌症抗原制造的。例如,在某些类型的白血病或淋巴瘤中,癌细胞有一种称为CD19的抗原。治疗这些癌症的CAR T细胞疗法是为了与CD19抗原结合,对不含CD19抗原的癌症无效。


接受CAR T细胞治疗


CAR T细胞治疗过程可能需要数周时间。


收集T细胞


首先,使用一种称为白细胞分离的方法从患者血液中去除白细胞(包括T细胞)。在此过程中,患者通常躺在床上或坐在躺椅上。需要两条静脉输液管,因为血液通过一条管线排出,白细胞分离出来,然后血液通过另一条管线返回体内。有时会使用一种称为中心静脉导管的特殊类型的静脉输液管,它内置两条静脉输液管。


在手术过程中,患者需要坐着或躺下2至3小时。有时在白细胞去除术中血钙水平会下降,这会导致麻木、刺痛或肌肉痉挛。这可以很容易地通过更换钙来治疗,钙可以通过口服或静脉注射。


制造汽车T细胞


去除白细胞后,分离T细胞,送往实验室,并通过添加特异性嵌合抗原受体(CAR)基因进行改变。这使他们成为汽车T细胞。然后这些细胞在实验室中生长和繁殖。可能需要几周的时间才能制造出这种治疗所需的大量CAR T细胞。


接受CAR T细胞输注


一旦制造出足够的CAR T细胞,它们将被送回患者体内。在CAR T细胞输注前几天,患者可能会接受化疗,以帮助降低其他免疫细胞的数量。这使CAR T细胞有更好的机会被激活以对抗癌症。这种化疗通常不是很强,因为CAR T细胞在有癌细胞攻击时效果最好。一旦CAR T细胞开始与癌细胞结合,它们的数量就会开始增加,并有助于摧毁更多的癌细胞。


认可的CAR T细胞疗法


CAR T细胞疗法被FDA批准用于治疗某些类型的淋巴瘤、白血病以及多发性骨髓瘤。CAR T细胞治疗通常在尝试其他类型的治疗后使用。


目前批准的CAR T细胞疗法包括:


Tisagenlecleucel,也称为tisa cel(Kymriah)


Axicabtagene ciloleucel,也称为axi-cel(叶斯卡塔)


Brexucabtagene autoleucel,也称为brexu cel(Tecartus)


liso-Tagene Maraluel,也称为liso-cel(Breyanzi)


Idecabtagene Vicluel,也称为ide cel(Abecma)


许多其他CAR T细胞疗法(以及类似类型的疗法)正在临床试验中进行研究,希望也能治疗其他类型的癌症。


可能的CAR T细胞治疗副作用


CAR T细胞疗法对某些难以治疗的癌症非常有效,但有时也会导致严重甚至危及生命的副作用。因此,它需要在经过专门培训的医疗中心使用,患者在获得CAR T细胞后需要被密切观察数周。


细胞因子释放综合征(CRS):随着CAR T细胞的增殖,它们可以向血液中释放大量称为细胞因子的化学物质,从而增强免疫系统。此版本的严重副作用可能包括:


高烧寒战


呼吸困难


严重恶心、呕吐和/或腹泻


感到头晕或头晕


头痛


心跳加快


感觉很累


肌肉和/或关节疼痛


随着医生在CAR T细胞治疗方面获得更多经验,他们正在学习如何早期识别CRS,以及如何治疗CRS。


神经系统问题:这种治疗有时会对神经系统产生严重影响,从而导致以下症状:


头痛


意识的变化


混乱或骚动


发作


颤抖或抽搐(震颤)


说话和理解困难


失去平衡


由于存在这些副作用的风险,通常建议成年患者在接受治疗后至少几周内不要驾驶、操作重型机械或进行任何其他潜在危险的活动。


其他严重副作用:CAR T细胞治疗的其他可能严重副作用包括:


输液过程中的过敏反应


血液中矿物质含量异常,如低钾、低钠或低磷


免疫系统减弱,严重感染的风险增加


低血细胞计数会增加感染、疲劳、瘀伤或出血的风险


如果您正在接受CAR T细胞治疗,立即向您的医疗团队报告任何副作用是非常重要的,因为通常有药物可以帮助治疗这些副作用。


原文标题:CAR T-cell Therapy and Its Side Effects,部分内容翻译可能有误,请以原文为准,本篇仅供参考。

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