双靶标CAR-T细胞——实体肿瘤的克星

2018-08-12 悠然生物探索

西雅图儿童医院最近开展了一项名为STRIvE-01的嵌合抗原受体（CAR-T）细胞免疫治疗试验，该试验适用于伴有EGFR蛋白表达的实体瘤儿童和青少年患者。在第1阶段试验中，双靶标的CAR-T细胞将更好地靶向儿童肉瘤、肾肿瘤和神经母细胞瘤等实体肿瘤中的EGFR蛋白。

不包括大脑的实体肿瘤约占所有儿童癌症的30％。肉瘤，一种在骨骼和软组织中发展的癌症；肾脏恶性肿瘤，包括肾母细胞瘤；神经母细胞瘤，一种在年轻神经细胞中形成的肿瘤，是儿童中诊断出的最常见的非中枢神经系统实体瘤。即使几十年来治疗方法的进步提高了患癌儿童的存活率，但当癌症复发或初始治疗无效时，这些实体肿瘤仍然是对标准疗法最具抵抗力的肿瘤之一。

“尽管现代疗法为实体瘤患儿提供了更深入的治疗或新的药物组合，但williamhill asia 却无力改善高危患儿群体的治疗效果。”西雅图儿童医院的肿瘤学家、STRIvE-01项目的领导者Katie Albert博士说道， “正是这些孩子，促使williamhill asia 研究新的治疗方法，以便治愈所有患者。”

虽然在西雅图儿童医院的临床试验中，CAR-T细胞在临床试验中显示出了治愈白血病儿童的希望，但在实体瘤上却面临更艰难的挑战。实体肿瘤存在于特殊的微环境中，这些微环境有助于它们逃避免疫系统，使得CAR-T细胞很难保持杀伤能力。

“为了使CAR-T疗法能有效对抗实体肿瘤，williamhill asia 不仅需要使CAR-T细胞进入肿瘤微环境，还需要确保它们能够存活并在那里茁壮成长。”Albert博士说。

为了构建STRIvE-01项目所需的CAR-T细胞，西雅图儿童研究所Ben Towne儿童癌症研究中心的Mike Jensen教授带领研究团队将对患者的T细胞进行重新编程，以靶向细胞表面表达异常的EGFR蛋白。在正常组织中，EGFR负责细胞生长和发育。当在恶性实体瘤中表达时，EGFR则使肿瘤细胞更具侵袭性和侵入性。

Katie Albert博士（左）和Mike Jensen教授（右）

通过使用名为EGFR806的抗体来武装CAR-T细胞，研究人员希望选择性地发现并破坏表达EGFR的实体瘤细胞，并限制其对正常组织的毒性。

参加第一组试验的儿童和年轻人将接受EGFR806武装的CAR-T细胞，试验将评估这种疗法的毒性并确定实验治疗的最大耐受剂量。完成安全性测试后，参加第二组试验的患者将接受重新编程的CAR-T细胞，它会同时靶向EGFR和一种名为CD19的蛋白，这是一种表达于B淋巴细胞的白细胞亚群上的蛋白质。

“通过包含靶向两种蛋白质的CAR-T细胞疗法，williamhill asia 在治疗实体肿瘤方面的研究又向前迈进了一步，抗癌T细胞可以在很短时间到达肿瘤组织。”Albert说， “基于williamhill asia 在白血病试验中的研究成果，williamhill asia 希望CD19的二级靶点能与 IBD%E8%AF%8A%E6%B2%BB%E8%BF%87%E7%A8%8B%E4%B8%AD%E7%9A%84%E8%AF%84%E4%BC%B0-Part%202" target="_blank">血液中的B淋巴细胞相互作用，以促进定向于EGFR的CAR-T细胞的扩增和其杀伤力。”

“williamhill asia 可能需要一系列治疗策略来操纵免疫环境，才能治愈难以治疗的实体瘤患者。”Albert博士说，“我很高兴有机会将williamhill asia 最先进的免疫治疗策略纳入这次实体肿瘤治疗计划，我希望能为更多家庭提供最有效和最全面的CAR-T细胞治疗方案，帮助治疗孩子的癌症。”

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2018-08-20 1e145228m78(暂无匿称)

a:￥CnTwb1llNAq￥

71 0
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2019-04-12 仁心济世

#CAR-#

41 0
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2018-08-15 kafei

学习学习谢谢

64 0
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2018-08-14 zhaojie88

#靶标#

45 0
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2018-08-14 weiz

#实体肿瘤#

47 0
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2018-08-12 Jackie Li

学习

73 0

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