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Internalization by Cells and Antitumor Activity of Antibodies and Immunotoxins Specific for the Heat Shock Protein 90 β Isoform
Biophysics Pub Date : 2021-03-11 , DOI: 10.1134/s0006350920060238
M. A. Zhmurina , V. V. Vrublevskaya , Y. Y. Skarga , V. S. Petrenko , V. K. Zhalimov , O. S. Morenkov

Mouse monoclonal antibodies to Hsp90β (β isoform of heat shock protein 90) have been shown to bind specifically to Hsp90β localized on the surface of tumor and nontransformed cells. After binding to the membrane-associated Hsp90β, the antibodies actively dissociated into the culture medium and were also internalized by the cells. An immunoconjugate based on the Hsp90β-specific antibody and the cytotoxic agent mertansine did not have high cytotoxic activity for tumor cells in vitro. Administration of Hsp90β-specific antibodies in mice did not affect the growth of the primary Lewis lung carcinoma, while tumor metastasis to the lungs decreased and the average lifespan of mice increased. The results indicate a certain therapeutic potential of antibodies to Hsp90β for the treatment of tumor diseases.



中文翻译:

细胞内在化以及对热休克蛋白90β亚型特异的抗体和免疫毒素的抗肿瘤活性

已经显示针对Hsp90β(热休克蛋白90的β亚型)的小鼠单克隆抗体特异性结合位于肿瘤和未转化细胞表面的Hsp90β。与膜相关的Hsp90β结合后,抗体主动解离到培养基中,并且也被细胞内化。基于Hsp90β特异性抗体和细胞毒剂美登素的免疫偶联物在体外对肿瘤细胞没有很高的细胞毒活性。在小鼠中施用Hsp90β特异性抗体不会影响原发性Lewis肺癌的生长,而向肺的肿瘤转移却减少了,小鼠的平均寿命也增加了。结果表明抗Hsp90β的抗体在治疗肿瘤疾病方面具有一定的治疗潜力。

更新日期:2021-03-11
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