Retaining Antibodies in Tumors with a Self-Assembling Injectable System
Retaining Antibodies in Tumors with a Self-Assembling Injectable System
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DOI：
10.1021/mp300504z
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发表时间：
2013-03-01
影响因子：
4.9
通讯作者：
Meng, Wilson S.
中科院分区：
文献类型：
--
作者：
Wen, Yi;Kolonich, Harold R.;Meng, Wilson S.
描述了设计用于在体内保留抗体分子的原位形成的可注射膜的性能。该系统需要肽两亲物（称为“EAK 16-II”和“EAKH 6”）和中间蛋白（抗H6抗体和蛋白A/G）的水性混合物，治疗性IgG分子通过该水性混合物共定位和定向。扫描电子显微照片显示IgG分子位于EAK 16-II/EAKH 6膜上。通过特异性相互作用捕获IgG，并在体外保持生物活性。在皮下给药至小鼠后，两亲性肽共组装成稳定的His-标签局部展示材料。该系统被证明保留在体内的荧光染料标记的IgG在两个上皮肿瘤细胞系。发现与系统共施用的IgG在4 T1小鼠乳腺肿瘤中保留长达120小时，而游离抗体在前24小时内被清除。在小鼠足垫中建立的B16黑色素瘤中也发现清除率降低。这些研究表明，固定化机制是有效的，在提高局部保留IgG在体内。可注射系统可用于增强免疫调节抗体在肿瘤中的递送。
The performance of an in situ-forming injectable membrane designed to retain antibody molecules in vivo is described. The system entails an aqueous mixture of peptide amphiphiles (referred to as"EAK16-II" and "EAKH6") and intermediate proteins (anti-H6 antibody and protein A/G) through which therapeutic IgG molecules are colocalized and oriented. Scanning electron micrographs show IgG molecules localized on the EAK16-II/EAKH6 membrane. IgG were captured via specific interactions and remained biologically active in vitro. Upon administration into mice subcutaneously, the amphiphilic peptides coassembled into stable His-tags displaying materials locally. The system was shown to retain in vivo a fluorescent dye-labeled IgG in two epithelial tumor lines. IgG coadministered with the system were found to remain in 4T1 mouse mammary tumors for up to 120 h, while free antibody was cleared within the first 24 h. Decreased clearance was also found in B16 melanoma established in mouse footpads. These studies demonstrated that the immobilizing mechanism was effective in enhancing the retention of IgG locally in vivo. The injectable system may be used to enhance the delivery of immune modulatory antibodies in tumors.