ENHANCED INVITRO TUMOR-CELL RETENTION AND INTERNALIZATION OF ANTIBODY DERIVATIZED WITH SYNTHETIC PEPTIDES
ENHANCED INVITRO TUMOR-CELL RETENTION AND INTERNALIZATION OF ANTIBODY DERIVATIZED WITH SYNTHETIC PEPTIDES
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DOI：
10.1021/bc00019a002
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发表时间：
1993-01-01
影响因子：
4.7
通讯作者：
FRITZBERG, AR
中科院分区：
文献类型：
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作者：
ANDERSON, DC;MANGER, R;FRITZBERG, AR
两种抗肿瘤单克隆抗体NR-ML-05和NR-LU-10的Fab片段已经用合成肽共价衍生化，所述合成肽设计为提供第二附着位点以增强其在肿瘤细胞上的保留。肽“GALA”的类似物，一种先前报道与不带电的脂质双层相互作用的两亲肽，当使用异双功能交联剂磺基-SMCC连接到Fab片段时，得到不同分子量和结合肽化学计量的抗体缀合物。这种连接的肽增强了NR-ML-05的Fab片段在FEMX人黑素瘤细胞上的保留和内化，但不增强NR-LU-10在HT-29人结肠癌细胞上的保留和内化，表明这种作用可能对个体肿瘤抗原-抗体系统具有特异性。该肽似乎增加缀合物与抗原阴性细胞的非特异性相互作用。还测试了其他膜活性肽。没有一个像“GALA”类似物一样有效。与NR-ML-05 Fab连接的合成离子通道肽表现出这些测试肽的最大增强内化。
The Fab fragments of two antitumor monoclonal antibodies, NR-ML-05 and NR-LU-10, have been covalently derivatized with synthetic peptides designed to provide secondary sites of attachment to enhance their retention on tumor cells. Analogs of the peptide ''GALA'', an amphipathic peptide previously reported to interact with uncharged lipid bilayers, gave antibody conjugates of different molecular weight and bound peptide stoichiometry when attached to Fab fragments using the heterobifunctional cross-linker sulfo-SMCC. This attached peptide enhanced the retention and internalization of Fab fragments of NR-ML-05 on FEMX human melanoma cells, but not of NR-LU-10 on HT-29 human colon carcinoma cells, indicating that this effect might be specific for individual tumor antigen-antibody systems. This peptide appeared to increase nonspecific interactions of the conjugate with antigen-negative cells. Other membrane-active peptides were also tested. None were as effective as the ''GALA'' analogs. A synthetic ion channel peptide attached to NR-ML-05 Fab exhibited the greatest enhanced internalization of these tested peptides.