Your browser doesn't support javascript.
loading
A new CHO (Chinese hamster ovary)-derived cell line expressing anti-TNFα monoclonal antibody with biosimilar potential.
Luchese, Mateus Dalcin; Lopes Dos Santos, Mariana; Garbuio, Angelica; Targino, Roselaine Campos; Mansueli, Carla Ploeger; Tsuruta, Lilian Rumi; Quintilio, Wagner; Moro, Ana Maria.
Afiliação
  • Luchese MD; Laboratório de Biofármacos em Células Animais, Instituto Butantan, Av. Vital Brasil 1500, São Paulo, SP, 05503-900, Brazil.
  • Lopes Dos Santos M; Laboratório de Biofármacos em Células Animais, Instituto Butantan, Av. Vital Brasil 1500, São Paulo, SP, 05503-900, Brazil.
  • Garbuio A; Laboratório de Biofármacos em Células Animais, Instituto Butantan, Av. Vital Brasil 1500, São Paulo, SP, 05503-900, Brazil.
  • Targino RC; Laboratório de Biofármacos em Células Animais, Instituto Butantan, Av. Vital Brasil 1500, São Paulo, SP, 05503-900, Brazil.
  • Mansueli CP; Laboratório de Biofármacos em Células Animais, Instituto Butantan, Av. Vital Brasil 1500, São Paulo, SP, 05503-900, Brazil.
  • Tsuruta LR; Laboratório de Biofármacos em Células Animais, Instituto Butantan, Av. Vital Brasil 1500, São Paulo, SP, 05503-900, Brazil.
  • Quintilio W; Laboratório de Biofármacos em Células Animais, Instituto Butantan, Av. Vital Brasil 1500, São Paulo, SP, 05503-900, Brazil.
  • Moro AM; Laboratório de Biofármacos em Células Animais, Instituto Butantan, Av. Vital Brasil 1500, São Paulo, SP, 05503-900, Brazil. ana.moro@butantan.gov.br.
Immunol Res ; 66(3): 392-405, 2018 06.
Article em En | MEDLINE | ID: mdl-29855993
Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine that mediates the homeostasis of immune responses; its exacerbated production is associated with the pathogenesis of autoimmune and chronic inflammatory diseases. Anti-TNFα drugs have revolutionized the treatment of inflammatory conditions such as rheumatoid arthritis and Crohn's disease. Currently, a worldwide race is on stage for the production of biosimilars moved by patent expiration of monoclonal antibodies (mAbs), such as anti-TNFα adalimumab. Our goal was to develop the first stage of an adalimumab biosimilar candidate with potential for national production, through the generation of a productive and stable cell line and assess its functionality. The robotic system ClonePix was used for screening and isolation of colonies from transfected CHO-S stable pools plated in semisolid medium. Selected clones were expanded based on growth and productivity. Purified mAbs from different clones were tested for binding and functional activity. The binding affinity of the denominated adabut clones to TNFα and FcRγ did not differ statistically when compared to reference adalimumab. One functional activity assay demonstrated the antibody neutralization capacity of the cytotoxicity induced by TNFα in L929 murine fibroblasts. A second assay confirmed adabut as an antagonist of the TNFα activity by the inhibition of the cell adhesion molecule expression in HUVEC cultures. The binding and functional activity analyses performed with selected adabut clones in comparison to reference adalimumab represent an important status of "non-inferiority," part of the process required for a biosimilar development. We generated and selected high-quality adabut clones which mAbs may be further developed as the first in-house made Brazilian biosimilar, demonstrating a success case for our incipient biotechnology industry, or also modified as biobetters, thus representing an innovative strategy for the patients' welfare.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Recombinantes de Fusão / Fator de Necrose Tumoral alfa / Medicamentos Biossimilares / Adalimumab / Anticorpos Monoclonais Limite: Animals / Humans Idioma: En Revista: Immunol Res Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Recombinantes de Fusão / Fator de Necrose Tumoral alfa / Medicamentos Biossimilares / Adalimumab / Anticorpos Monoclonais Limite: Animals / Humans Idioma: En Revista: Immunol Res Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos