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Internalization by Cells and Antitumor Activity of Antibodies and Immunotoxins Specific for the Heat Shock Protein 90 β Isoform

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Abstract

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.

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Correspondence to M. A. Zhmurina.

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All applicable international, national and institutional principles for the care and use of animals in the performance of the work have been observed.

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Translated by E. Puchkov

Abbreviations: Hsp90, heat shock protein 90; eHsp90, extracellular Hsp90; DMEM, Dulbecco’s Modified Eagle Medium; FBS, fetal bovine serum; ELISA, enzyme-linked immunosorbent assay; PBS, phosphate-buffered saline.

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Zhmurina, M.A., Vrublevskaya, V.V., Skarga, Y.Y. et al. Internalization by Cells and Antitumor Activity of Antibodies and Immunotoxins Specific for the Heat Shock Protein 90 β Isoform. BIOPHYSICS 65, 951–957 (2020). https://doi.org/10.1134/S0006350920060238

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  • DOI: https://doi.org/10.1134/S0006350920060238

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