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CLIN CANCER RES ：Anti-NaPi2b抗体药物偶联物作为非小细胞肺癌和卵巢癌治疗的临床前景

2015-07-09 范伟译 MedSci原创

Anti-NaPi2b抗体药物共轭物非小细胞肺癌卵巢癌
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目的：抗体药物偶联物(ADCs)有选择性的输送细胞毒性药物到细胞，表达易进入的靶目抗原。这里我们偶联单甲基阿里他汀 E(MMAE)到抗体识别SLC34A2基因产物NaPi2b，II型磷酸钠协同转运蛋白，其在肺部、卵巢、甲状腺肿瘤表面高度表达，也在正常的肺细胞中有表达。本研究评估临床前研究的有效性和安全性。实验设计：抗NaPi2b 抗体药物偶联物ADC的疗效通过卵巢癌小鼠和非小细胞肺癌(NSCLC)

目的：抗体药物偶联物(ADCs)有选择性的输送细胞毒性药物到细胞，表达易进入的靶目抗原。这里我们偶联单甲基阿里他汀 E(MMAE)到抗体识别SLC34A2基因产物NaPi2b，II型磷酸钠协同转运蛋白，其在肺部、卵巢、甲状腺肿瘤表面高度表达，也在正常的肺细胞中有表达。本研究评估临床前研究的有效性和安全性。

实验设计：抗NaPi2b 抗体药物偶联物ADC的疗效通过卵巢癌小鼠和非小细胞肺癌(NSCLC)肿瘤异种移植模型进行评估，其毒性在老鼠和猕猴上进行评价。

结果：这里我们显示了抗NaPi2b 抗体药物偶联物ADC在卵巢癌小鼠和非小细胞肺癌(NSCLC)肿瘤异种移植模型上是有效的，在老鼠和猕猴上采用过度治疗剂量有良好的耐受性。尽管在非人类灵长类动物正常肺部有高水平的表达，交叉反应的抗体药物偶联物ADC表现出可接受的安全性，且剂量限制毒性与正常组织靶标的表达无关。正常肺细胞非增殖的特性，MMAE的抗-增殖机制，可能减轻潜在的正常组织表达的不利因素。

结论：总的来说，我们的临床前结果表明，抗体药物共轭物靶标于NaPi2b为非小细胞肺癌、卵巢癌提供了一种有效的新疗法，目前正在往临床方向发展。

原始出处：

Kedan Lin, Bonnee Rubinfeld, Crystal Zhang, Ron Firestein,et al.Development of an AntiNaPi2b (SLC34A2) Antibody |Drug Conjugate as a Therapeutic for NonSmall Cell Lung and Ovarian Cancers.CLIN CANCER RES .July 8, 2015; doi: 10.1158/1078-0432.CCR-14-3383

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    2015-09-10 lingaifan

    #非小细胞#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=2059509, encodeId=a9e1205950963, content=<a href='/topic/show?id=2cc599381bd' target=_blank style='color:#2F92EE;'>#非小细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99381, encryptionId=2cc599381bd, topicName=非小细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Thu Sep 10 07:14:00 CST 2015, time=2015-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2016153, encodeId=52b72016153e5, content=<a href='/topic/show?id=d0565520072' target=_blank style='color:#2F92EE;'>#抗体药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55200, encryptionId=d0565520072, topicName=抗体药物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e6a1280, createdName=zhanglin3079, createdTime=Sat Nov 21 21:14:00 CST 2015, time=2015-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1957600, encodeId=9270195e600a6, content=<a href='/topic/show?id=a09c551998a' target=_blank style='color:#2F92EE;'>#抗体药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55199, encryptionId=a09c551998a, topicName=抗体药)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=793a2500200, createdName=12498e5fm12(暂无昵称), createdTime=Wed Feb 17 02:14:00 CST 2016, time=2016-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=32503, encodeId=3ce632503f5, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=195, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee0d1618732, createdName=huaxipanxing, createdTime=Sun Jul 12 20:09:00 CST 2015, time=2015-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1413818, encodeId=a967141381868, content=<a href='/topic/show?id=ce4a55202f0' target=_blank style='color:#2F92EE;'>#抗体药物偶联物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55202, encryptionId=ce4a55202f0, topicName=抗体药物偶联物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f5ea3025344, createdName=chendoc243, createdTime=Sat Jul 11 03:14:00 CST 2015, time=2015-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=32085, encodeId=2858320857f, content=需要临床实验吗。13640291462, beContent=null, objectType=article, channel=null, level=null, likeNumber=163, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bdda1631721, createdName=YINJUAN885, createdTime=Thu Jul 09 20:26:00 CST 2015, time=2015-07-09, status=1, ipAttribution=)]
    2015-11-21 zhanglin3079

    #抗体药物#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=2059509, encodeId=a9e1205950963, content=<a href='/topic/show?id=2cc599381bd' target=_blank style='color:#2F92EE;'>#非小细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99381, encryptionId=2cc599381bd, topicName=非小细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Thu Sep 10 07:14:00 CST 2015, time=2015-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2016153, encodeId=52b72016153e5, content=<a href='/topic/show?id=d0565520072' target=_blank style='color:#2F92EE;'>#抗体药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55200, encryptionId=d0565520072, topicName=抗体药物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e6a1280, createdName=zhanglin3079, createdTime=Sat Nov 21 21:14:00 CST 2015, time=2015-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1957600, encodeId=9270195e600a6, content=<a href='/topic/show?id=a09c551998a' target=_blank style='color:#2F92EE;'>#抗体药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55199, encryptionId=a09c551998a, topicName=抗体药)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=793a2500200, createdName=12498e5fm12(暂无昵称), createdTime=Wed Feb 17 02:14:00 CST 2016, time=2016-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=32503, encodeId=3ce632503f5, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=195, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee0d1618732, createdName=huaxipanxing, createdTime=Sun Jul 12 20:09:00 CST 2015, time=2015-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1413818, encodeId=a967141381868, content=<a href='/topic/show?id=ce4a55202f0' target=_blank style='color:#2F92EE;'>#抗体药物偶联物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55202, encryptionId=ce4a55202f0, topicName=抗体药物偶联物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f5ea3025344, createdName=chendoc243, createdTime=Sat Jul 11 03:14:00 CST 2015, time=2015-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=32085, encodeId=2858320857f, content=需要临床实验吗。13640291462, beContent=null, objectType=article, channel=null, level=null, likeNumber=163, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bdda1631721, createdName=YINJUAN885, createdTime=Thu Jul 09 20:26:00 CST 2015, time=2015-07-09, status=1, ipAttribution=)]
    2016-02-17 12498e5fm12(暂无昵称)

    #抗体药#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=2059509, encodeId=a9e1205950963, content=<a href='/topic/show?id=2cc599381bd' target=_blank style='color:#2F92EE;'>#非小细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99381, encryptionId=2cc599381bd, topicName=非小细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Thu Sep 10 07:14:00 CST 2015, time=2015-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2016153, encodeId=52b72016153e5, content=<a href='/topic/show?id=d0565520072' target=_blank style='color:#2F92EE;'>#抗体药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55200, encryptionId=d0565520072, topicName=抗体药物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e6a1280, createdName=zhanglin3079, createdTime=Sat Nov 21 21:14:00 CST 2015, time=2015-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1957600, encodeId=9270195e600a6, content=<a href='/topic/show?id=a09c551998a' target=_blank style='color:#2F92EE;'>#抗体药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55199, encryptionId=a09c551998a, topicName=抗体药)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=793a2500200, createdName=12498e5fm12(暂无昵称), createdTime=Wed Feb 17 02:14:00 CST 2016, time=2016-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=32503, encodeId=3ce632503f5, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=195, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee0d1618732, createdName=huaxipanxing, createdTime=Sun Jul 12 20:09:00 CST 2015, time=2015-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1413818, encodeId=a967141381868, content=<a href='/topic/show?id=ce4a55202f0' target=_blank style='color:#2F92EE;'>#抗体药物偶联物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55202, encryptionId=ce4a55202f0, topicName=抗体药物偶联物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f5ea3025344, createdName=chendoc243, createdTime=Sat Jul 11 03:14:00 CST 2015, time=2015-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=32085, encodeId=2858320857f, content=需要临床实验吗。13640291462, beContent=null, objectType=article, channel=null, level=null, likeNumber=163, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bdda1631721, createdName=YINJUAN885, createdTime=Thu Jul 09 20:26:00 CST 2015, time=2015-07-09, status=1, ipAttribution=)]
    2015-07-12 huaxipanxing

    看看

    0

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    2015-07-11 chendoc243

    #抗体药物偶联物#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=2059509, encodeId=a9e1205950963, content=<a href='/topic/show?id=2cc599381bd' target=_blank style='color:#2F92EE;'>#非小细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99381, encryptionId=2cc599381bd, topicName=非小细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Thu Sep 10 07:14:00 CST 2015, time=2015-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2016153, encodeId=52b72016153e5, content=<a href='/topic/show?id=d0565520072' target=_blank style='color:#2F92EE;'>#抗体药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55200, encryptionId=d0565520072, topicName=抗体药物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e6a1280, createdName=zhanglin3079, createdTime=Sat Nov 21 21:14:00 CST 2015, time=2015-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1957600, encodeId=9270195e600a6, content=<a href='/topic/show?id=a09c551998a' target=_blank style='color:#2F92EE;'>#抗体药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55199, encryptionId=a09c551998a, topicName=抗体药)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=793a2500200, createdName=12498e5fm12(暂无昵称), createdTime=Wed Feb 17 02:14:00 CST 2016, time=2016-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=32503, encodeId=3ce632503f5, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=195, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee0d1618732, createdName=huaxipanxing, createdTime=Sun Jul 12 20:09:00 CST 2015, time=2015-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1413818, encodeId=a967141381868, content=<a href='/topic/show?id=ce4a55202f0' target=_blank style='color:#2F92EE;'>#抗体药物偶联物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55202, encryptionId=ce4a55202f0, topicName=抗体药物偶联物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f5ea3025344, createdName=chendoc243, createdTime=Sat Jul 11 03:14:00 CST 2015, time=2015-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=32085, encodeId=2858320857f, content=需要临床实验吗。13640291462, beContent=null, objectType=article, channel=null, level=null, likeNumber=163, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bdda1631721, createdName=YINJUAN885, createdTime=Thu Jul 09 20:26:00 CST 2015, time=2015-07-09, status=1, ipAttribution=)]
    2015-07-09 YINJUAN885

    需要临床实验吗。13640291462

    0

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