A non-internalizing antibody-drug conjugate based on an anthracycline payload displays potent therapeutic activity in vivo.
A non-internalizing antibody-drug conjugate based on an anthracycline payload displays potent therapeutic activity in vivo.
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DOI：
10.1016/j.jconrel.2017.08.040
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发表时间：
2017-10-28
期刊：
影响因子：
--
通讯作者：
Neri D
中科院分区：
文献类型：
--
作者：
Dal Corso A;Gébleux R;Murer P;Soltermann A;Neri D
抗体-药物结合物通常被认为是至关重要的依赖于内化到癌细胞的治疗活性。在这里，我们展示了一种基于Tenascin-C选择性剪接A1结构域的F16抗体的非内在化抗体-药物结合物，当配备蒽环类药物PNU159682时，它介导了一种强大的治疗活性。这种多肽连接物将位于特定半胱氨酸残基的Ig G形式的F16抗体连接到药物上，在血清中稳定，但可以被濒临死亡的肿瘤细胞释放的蛋白酶有效地切割在内皮下细胞外基质中。结果表明，非内在化抗体-药物偶联物在癌症治疗中的潜在适用性可能比先前假设的更广泛。
Antibody-drug conjugates are generally believed to crucially rely on internalization into cancer cells for therapeutic activity. Here, we show that a non-internalizing antibody-drug conjugate, based on the F16 antibody specific to the alternatively spliced A1 domain of tenascin-C, mediates a potent therapeutic activity when equipped with the anthracycline PNU159682. The peptide linker, connecting the F16 antibody in IgG format at a specific cysteine residue to the drug, was stable in serum but could be efficiently cleaved in the subendothelial extracellular matrix by proteases released by the dying tumor cells. The results indicate that there may be a broader potential applicability of non-internalizing antibody-drug conjugates for cancer therapy than what had previously been assumed.
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影响因子：
12.4
作者：
Choi KY;Swierczewska M;Lee S;Chen X
通讯作者：
Chen X
影响因子：
5.7
作者：
Gébleux R;Wulhfard S;Casi G;Neri D
通讯作者：
Neri D
影响因子：
5.7
作者：
Cazzamalli S;Dal Corso A;Neri D
通讯作者：
Neri D
DOI：
10.1007/s00259-013-2658-6
发表时间：
2014-05-01
影响因子：
9.1
作者：
Aloj, Luigi;D'Ambrosio, Laura;Lastoria, Secondo
通讯作者：
Lastoria, Secondo
影响因子：
4.7
作者：
Doronina, SO;Mendelsohn, BA;Senter, PD
通讯作者：
Senter, PD