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CLIN CANCER RES：Toca511应用于患者时具有安全性和活性

2018-10-22 MedSci MedSci原创

Toca511安全性活性
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Toca 511是编码胞嘧啶脱氨酶的γ逆转录病毒复制载体，可以选择性地感染肿瘤细胞并将5-氟胞嘧啶转化为抗肿瘤的药物5-氟尿嘧啶，5-氟尿嘧啶直接杀死肿瘤细胞并刺激抗肿瘤免疫应答。CLIN CANCER RES近期发表了一篇文章，对复发性高级别胶质瘤的I期临床试验进行临床监测，对患者标本进行了大量的分子分析以了解载体的结局。

Toca 511是编码胞嘧啶脱氨酶的γ逆转录病毒复制载体，可以选择性地感染肿瘤细胞并将5-氟胞嘧啶转化为抗肿瘤的药物5-氟尿嘧啶，5-氟尿嘧啶直接杀死肿瘤细胞并刺激抗肿瘤免疫应答。CLIN CANCER RES近期发表了一篇文章，对复发性高级别胶质瘤的I期临床试验进行临床监测，对患者标本进行了大量的分子分析以了解载体的结局。

三项I期研究共纳入127名高级别胶质瘤患者，患者接受Toca 511和Toca FC（缓释5-氟胞嘧啶）治疗。作者测量了患者体液和肿瘤样品中的Toca 511 RNA和DNA水平以评估肿瘤特异性。绘制了Toca 511整合位点，并对可检测到病毒的患者样本的Toca 511基因组进行了测序。作者还对一例患者的不同组织样本中的Toca 511水平进行了检测。研究结果表明，绝大部分的肿瘤样本中都可以检测到整合的Toca 511，仅在一小部分患者的血液中即时检测到。没有证据表明整合了Toca 511 DNA的细胞出现克隆扩增。Toca 511序列谱表明大多数突变是由逆转录过程的APOBEC胞苷脱氨酶引起的。对于特定患者的不同组织样品的检测确认了Toca 511的肿瘤选择性。

文章最后认为，Toca 511和Toca FC治疗与克隆扩增无关。该载体有肿瘤选择性，患者接受Toca 511注射后持续有效。

原始出处：

Daniel J. Hogan, Jay-Jiguang Zhu, et al. Molecular Analyses Support the Safety and Activity of Retroviral Replicating Vector Toca 511 in Patients. CLIN CANCER RES. October 2018 doi: 10.1158/1078-0432.CCR-18-0619 

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    2019-05-09 天堂的云

    #Toca511#

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    2019-04-25 wangyang7958

    #Toca#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=2049805, encodeId=a2c82049805b1, content=<a href='/topic/show?id=d3241e6155d' target=_blank style='color:#2F92EE;'>#Toca511#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17615, encryptionId=d3241e6155d, topicName=Toca511)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=68f2317, createdName=天堂的云, createdTime=Thu May 09 18:07:00 CST 2019, time=2019-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2079678, encodeId=27b520e96786c, content=<a href='/topic/show?id=71f81e61433' target=_blank style='color:#2F92EE;'>#Toca#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17614, encryptionId=71f81e61433, topicName=Toca)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=267e204, createdName=wangyang7958, createdTime=Thu Apr 25 20:07:00 CST 2019, time=2019-04-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1927925, encodeId=7932192e925bc, content=<a href='/topic/show?id=f7fb13216dc' target=_blank style='color:#2F92EE;'>#OCA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13216, encryptionId=f7fb13216dc, topicName=OCA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c39f145, createdName=smlt2008, createdTime=Wed Aug 21 23:07:00 CST 2019, time=2019-08-21, status=1, ipAttribution=)]
    2019-08-21 smlt2008

    #OCA#

    0