دورية أكاديمية
Initial development of biosimilar immune checkpoint blockers using HEK293 cells.
| العنوان: | Initial development of biosimilar immune checkpoint blockers using HEK293 cells. |
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| المؤلفون: | Ramos MB; Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., Araújo AEV; Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., Pestana CP; Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., Ano Bom APD; Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., Bastos RC; Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., de Almeida Oliveira A; Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., da Costa Neves PC; Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., da Silva Junior HC; Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil. Electronic address: haroldo.cid@bio.fiocruz.br. |
| المصدر: | Protein expression and purification [Protein Expr Purif] 2020 Jun; Vol. 170, pp. 105596. Date of Electronic Publication: 2020 Feb 07. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 9101496 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0279 (Electronic) Linking ISSN: 10465928 NLM ISO Abbreviation: Protein Expr Purif Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Orlando, FL : Academic Press Original Publication: San Diego : Academic Press, c1990- |
| مواضيع طبية MeSH: | Antibodies, Monoclonal/*pharmacology , Biosimilar Pharmaceuticals/*pharmacology , Immune Checkpoint Inhibitors/*pharmacology , Immune Checkpoint Proteins/*genetics , Immunoglobulin Heavy Chains/*pharmacology , Immunoglobulin Light Chains/*pharmacology, Antibodies, Monoclonal/biosynthesis ; Antibody Affinity ; Antibody Specificity ; Biosimilar Pharmaceuticals/metabolism ; Chromatography, Affinity ; Genetic Vectors/chemistry ; Genetic Vectors/metabolism ; HEK293 Cells ; Humans ; Immune Checkpoint Inhibitors/immunology ; Immune Checkpoint Proteins/immunology ; Immunoglobulin Heavy Chains/biosynthesis ; Immunoglobulin Light Chains/biosynthesis ; Isoelectric Focusing |
| مستخلص: | Antibodies that block interaction of immune checkpoint receptors with its ligands have revolutionized the treatment of several cancers. Despite the success of this approach, the high cost has been restricted the use of this class of drugs. In this context, the development of biosimilar can be an important strategy for reducing prices and expanding access after patent has been dropped. Here, we evaluated the use of HEK293 cells for transient expression of an immune checkpoint-blocking antibody as a first step for biosimilar development. Antibody light and heavy chain genes were cloned into pCI-neo vector and transiently expressed in HEK293 cells. The culture supernatant was then subjected to protein A affinity chromatography, which allowed to obtain the antibody with high homogeneity. For physicochemical comparability, biosimilar antibody and reference drug were analyzed by SDS-PAGE, isoelectric focusing, circular dichroism and fluorescence spectroscopy. The results indicated that the both antibodies have a high degree of structural similarity. Lastly, the biosimilar antibody binding capacity to target receptor was shown to be similar to reference product in ELISA and flow cytometry assays. These data demonstrate that the HEK293 system can be used as an important tool for candidate selection and early development of biosimilar antibodies. Competing Interests: Declaration of competing interest The authors declare no financial or commercial conflict of interest. (Copyright © 2020 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Biosimilar; Cancer; Checkpoint; Expression; HEK; Transient |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) 0 (Biosimilar Pharmaceuticals) 0 (Immune Checkpoint Inhibitors) 0 (Immune Checkpoint Proteins) 0 (Immunoglobulin Heavy Chains) 0 (Immunoglobulin Light Chains) |
| تواريخ الأحداث: | Date Created: 20200210 Date Completed: 20210107 Latest Revision: 20210107 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.pep.2020.105596 |
| PMID: | 32036001 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1096-0279 |
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| DOI: | 10.1016/j.pep.2020.105596 |