Nat Med :免疫疗法新突破!人体实验数据揭示CAR-NKT疗法治疗实体瘤的潜力

2020-10-22 探索菌 生物探索

免疫疗法是当下肿瘤治疗领域最具前景的发展方向之一,其中,CAR-T疗法更是百花丛中一枝独秀。然而,尽管该疗法在血液肿瘤治疗中表现出惊人疗效,在实体瘤治疗中却频频受挫。

免疫疗法是当下肿瘤治疗领域最具前景的发展方向之一,其中,CAR-T疗法更是百花丛中一枝独秀。然而,尽管该疗法在血液肿瘤治疗中表现出惊人疗效,在实体瘤治疗中却频频受挫。

最近,《Nature Medicine》发布的一篇文章为增强CAR定向癌症免疫疗法提供了新的机会,也为实体瘤治疗带来了新的突破。

这项由贝勒医学院和北卡罗来纳大学教堂山分校的研究人员带来的1期临床实验中期报告显示,通过基因改造使人类NKT细胞表达可特异性识别和攻击神经母细胞瘤(NB)的GD2特异性CAR(嵌合抗原受体)以及可支持NKT细胞生存的白细胞介素-15(IL-15),或许是抗击癌症的重要手段。3名接受该疗法的NB患者中,1人获得客观缓解,骨转移病灶消退。

自然杀伤T细胞(NKT)是一种表面既有T细胞受体TCR,又有NK细胞受体的特殊T细胞亚群。先前的研究表明,NKT细胞具有一系列的抗肿瘤活性,并且这类细胞的活化能够间接促进由NK和T细胞介导的抗肿瘤反应。

尽管优势明显,但NKT细胞在血液中的含量非常少,同时NKT细胞对抗肿瘤的方式大多是间接性的。于是,研究人员使用CAR对患者的NKT细胞进行了“武装”,使之能够直接攻击肿瘤,同时“配备”白细胞介素-15(IL-15)提高这些细胞的生存能力。

经过处理,3名患者的NKT细胞纯度均在90%以上。研究人员将这些细胞分别在体外培养了15天(患者1)、14天(患者2)和9天(患者3),然后输注回患者体内。结果表明,所有患者CAR-NKT细胞耐受性良好。在4周评估期内,患者外周血NKT细胞扩增频率和绝对数量均高于基线水平。

CAR-NKT细胞在患者体内的扩张和持续性

不过,细胞在体外的培养时间可能影响了CAR-NKT细胞的体内扩增效率。输注相应细胞产品后,患者3 的CAR-NKT细胞绝对数最高,而患者1的CAR-NKT细胞绝对数最低。

随后,研究人员进行了一系列肿瘤激发试验,每5天给3名患者的CAR-NKT细胞补充一次NB细胞,持续5次。在补充了3次NB细胞后,患者1的CAR-NKT细胞逐渐失去细胞毒性活性,而患者2和患者3的CAR-NKT细胞在整个期间仍保持杀死NB细胞的能力以及更强的增殖反应。

进一步实验中,研究人员发现,在患者的外周血中可以检测到CAR-IL15 NKT细胞,这些细胞在输注后扩增并转移到骨转移灶和骨髓,发挥抗肿瘤活性并诱导肿瘤消退。在3名患者中,有1名患者至少50%的骨转移病灶被消除。

贝勒医学院和德克萨斯儿童癌症中心的儿科肿瘤学家Leonid S. Metelitsa说:“临床实验表明,利用具有天然抗肿瘤能力的免疫细胞,通过设计合成受体来增强它们的抗肿瘤能力是可能的,这为应用这种策略对抗难以治疗的实体肿瘤带来了新的希望。”

总之,这项研究表明,CAR-NKT细胞可以扩展到临床规模,并可以安全地用于治疗癌症患者。目前,研究人员已经将研发的NKT平台授权给Kuur Therapeutics公司,以推进临床应用。

原始出处:

Andras Heczey, Amy N Courtney, Antonino Montalbano,et al.Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: an interim analysis.Nat Med. 2020 Oct 12. doi: 10.1038/s41591-020-1074-2.

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    2021-01-21 xuruicheng
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    2021-02-04 zxxiang
  4. [GetPortalCommentsPageByObjectIdResponse(id=1751742, encodeId=29801e5174295, content=<a href='/topic/show?id=ba8612842b3' target=_blank style='color:#2F92EE;'>#NKT#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12842, encryptionId=ba8612842b3, topicName=NKT)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=74e936405699, createdName=xuruicheng, createdTime=Thu Jan 21 04:25:42 CST 2021, time=2021-01-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1744748, encodeId=59b81e4474810, content=<a href='/topic/show?id=4f2c246e23b' target=_blank style='color:#2F92EE;'>#人体实验#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24672, encryptionId=4f2c246e23b, topicName=人体实验)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1aa635427520, createdName=echonoir, createdTime=Sat May 22 15:25:42 CST 2021, time=2021-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1725043, encodeId=f9d11e25043bb, content=<a href='/topic/show?id=9ee758586bb' target=_blank style='color:#2F92EE;'>#新突破#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58586, encryptionId=9ee758586bb, topicName=新突破)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=792a33728807, createdName=zxxiang, createdTime=Thu Feb 04 15:25:42 CST 2021, time=2021-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884742, encodeId=df871884e4286, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Fri Aug 06 14:25:42 CST 2021, time=2021-08-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1946222, encodeId=aa57194622261, content=<a href='/topic/show?id=6826406122' target=_blank style='color:#2F92EE;'>#CAR-NKT#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4061, encryptionId=6826406122, topicName=CAR-NKT)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Tue Apr 13 05:25:42 CST 2021, time=2021-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1781389, encodeId=0eea1e81389d7, content=<a href='/topic/show?id=8ce8405907' target=_blank style='color:#2F92EE;'>#CAR-#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4059, encryptionId=8ce8405907, topicName=CAR-)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Sat Mar 20 06:25:42 CST 2021, time=2021-03-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1610761, encodeId=45821610e614a, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Sat Oct 24 03:25:42 CST 2020, time=2020-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=893872, encodeId=1f518938e22b, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f6005191681, createdName=1037657937_23630378, createdTime=Thu Oct 22 23:43:27 CST 2020, time=2020-10-22, status=1, ipAttribution=)]
    2021-08-06 liye789132251
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    2021-03-20 仁者大医
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    2020-10-22 1037657937_23630378

    学习了

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