The biological activity of bispecific trastuzumab/pertuzumab plant biosimilars may be drastically boosted by disulfiram increasing formaldehyde accumulation in cancer cells
| Autor: | Anastasia V. Shindyapina, Yuri L. Dorokhov, Fedor A. Lipskerov, Tatiana E. Byalik, V. S. Kosorukov, Ekaterina V. Sheshukova, Polina S. Shpudeiko, E. N. Kosobokova, Tatiana V. Komarova |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_treatment
lcsh:Medicine Antibodies Monoclonal Humanized Epitope Article Applied immunology Breast cancer Trastuzumab Cell Line Tumor Formaldehyde Neoplasms Disulfiram medicine Humans lcsh:Science Biosimilar Pharmaceuticals Cell Proliferation Multidisciplinary Cell growth Chemistry lcsh:R Immunotherapy Cancer cell Cancer research lcsh:Q Pertuzumab Drug Screening Assays Antitumor Adjuvant medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) |
| ISSN: | 2045-2322 |
| Popis: | Studies of breast cancer therapy have examined the improvement of bispecific trastuzumab/pertuzumab antibodies interacting simultaneously with two different epitopes of the human epidermal growth factor receptor 2 (HER2). Here, we describe the creation and production of plant-made bispecific antibodies based on trastuzumab and pertuzumab plant biosimilars (bi-TPB-PPB). Using surface plasmon resonance analysis of bi-TPB-PPB antibodies binding with the HER2 extracellular domain, we showed that the obtained Kd values were within the limits accepted for modified trastuzumab and pertuzumab. Despite the ability of bi-TPB-PPB antibodies to bind to Fcγ receptor IIIa and HER2 oncoprotein on the cell surface, a proliferation inhibition assay did not reveal any effect until α1,3-fucose and β1,2-xylose in the Asn297-linked glycan were removed. Another approach to activating bi-TPB-PPB may be associated with the use of disulfiram (DSF) a known aldehyde dehydrogenase 2 (ALDH2) inhibitor. We found that disulfiram is capable of killing breast cancer cells with simultaneous formaldehyde accumulation. Furthermore, we investigated the capacity of DSF to act as an adjuvant for bi-TPB-PPB antibodies. Although the content of ALDH2 mRNA was decreased after BT-474 cell treatment with antibodies, we only observed cell proliferation inhibiting activity of bi-TPB-PPB in the presence of disulfiram. We concluded that disulfiram can serve as a booster and adjuvant for anticancer immunotherapy. |
| Databáze: | OpenAIRE |
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