Anti-cancer Antibody Trastuzumab-Melanotransferrin Conjugate (BT2111) for the Treatment of Metastatic HER2+ Breast Cancer Tumors in the Brain: an In-Vivo Study.
Anti-cancer Antibody Trastuzumab-Melanotransferrin Conjugate (BT2111) for the Treatment of Metastatic HER2+ Breast Cancer Tumors in the Brain: an In-Vivo Study.
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抗癌抗体曲妥珠单抗 - 甲状腺素铁蛋白共轭物（BT2111）用于治疗大脑中的转移性HER2+乳腺癌肿瘤：一项体内研究。
DOI：
10.1007/s11095-016-2015-0
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发表时间：
2016-12
影响因子：
3.7
通讯作者：
Lockman PR
中科院分区：
文献类型：
--
作者：
Nounou MI;Adkins CE;Rubinchik E;Terrell-Hall TB;Afroz M;Vitalis T;Gabathuler R;Tian MM;Lockman PR
通过测量转移性人HER 2+乳腺癌肿瘤数量和大小的减少，研究了人黑转铁蛋白（hMTf）在缀合后（以曲妥珠单抗-黑转铁蛋白缀合物，BT 2111缀合物的形式）在大脑中携带治疗浓度的曲妥珠单抗（BTA）的能力。乳腺癌脑转移的临床前模型。将人转移性脑寻找乳腺癌细胞注射到NuNu小鼠（每组n=6-12）中，然后这些小鼠发生实验性脑转移。分析了药物摄取与转移灶大小和血肿瘤屏障通透性的关系。为了研究针对脑转移瘤的体内活性，在转移性癌细胞的心内注射后，每两周施用等摩尔剂量的缀合物和独立组中的相关对照（hMTF和BTA）。与对照组相比，曲妥珠单抗-黑转铁蛋白偶联物（BT 2111）使脑中临床前人HER 2+乳腺癌转移的数量减少了68%。治疗后残留的肿瘤比对照组小46%。相比之下，单独使用BTA对减少转移瘤数量没有影响，并且仅与转移瘤大小的最小减少相关。结果表明，新的曲妥珠单抗-黑转铁蛋白缀合物（BT 2111）可用于治疗脑转移，并验证hMTF作为抗体转运穿过血脑屏障（BBB）的潜在载体。
The ability of human melanotransferrin (hMTf) to carry a therapeutic concentration of trastuzumab (BTA) in the brain after conjugation (in the form of trastuzumab-melanotransferrin conjugate, BT2111 conjugate) was investigated by measuring the reduction of the number and size of metastatic human HER2+ breast cancer tumors in a preclinical model of brain metastases of breast cancer. Human metastatic brain seeking breast cancer cells were injected in NuNu mice (n=6–12 per group) which then developed experimental brain metastases. Drug uptake was analyzed in relation to metastasis size and blood-tumor barrier permeability. To investigate in-vivo activity against brain metastases, equimolar doses of the conjugate, and relevant controls (hMTF and BTA) in separate groups were administered biweekly after intracardiac injection of the metastatic cancer cells. The trastuzumab-melanotransferrin conjugate (BT2111) reduced the number of preclinical human HER2+ breast cancer metastases in the brain by 68% compared to control groups. Tumors which remained after treatment were 46% smaller than the control groups. In contrast, BTA alone had no effect on reducing number of metastases, and was associated with only a minimal reduction in metastasis size. The results suggest the novel trastuzumab-melanotransferrin conjugate (BT2111) may have utility in treating brain metastasis and validate hMTf as a potential vector for antibody transport across the Blood Brain Barrier (BBB).