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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 Fc\u03b3 receptor\u00a0IIIa and HER2 oncoprotein on the cell surface, a proliferation inhibition assay did not reveal any effect until \u03b11,3-fucose and \u03b21,2-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.<\/jats:p>","DOI":"10.1038\/s41598-019-52507-9","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T11:05:29Z","timestamp":1573124729000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The biological activity of bispecific trastuzumab\/pertuzumab plant biosimilars may be drastically boosted by disulfiram increasing formaldehyde accumulation in cancer cells"],"prefix":"10.1038","volume":"9","author":[{"given":"Tatiana V.","family":"Komarova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina V.","family":"Sheshukova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina N.","family":"Kosobokova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vyacheslav S.","family":"Kosorukov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia V.","family":"Shindyapina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fedor A.","family":"Lipskerov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina S.","family":"Shpudeiko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana E.","family":"Byalik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4066-8940","authenticated-orcid":false,"given":"Yuri L.","family":"Dorokhov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,7]]},"reference":[{"key":"52507_CR1","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1146\/annurev.cb.10.110194.001343","volume":"10","author":"P van der Geer","year":"1994","unstructured":"van der Geer, P., Hunter, T. & Lindberg, R. 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