title: Extensive preclinical evaluation of an infliximab biosimilar candidate.
abstract: Infliximab is therapeutic monoclonal antibody (mAb) against TNF-α employed in the treatment of immunoinflammatory diseases. The development of biosimilar mAbs is a global strategy to increase drug accessibility and reduce therapy-associated costs. Herein we compared key physicochemical characteristics and biological activities produced by infliximab and infliximab-Probiomed in order to identify functionally relevant differences between the mAbs. Binding of infliximab-Probiomed to TNF-α was specific and had kinetics comparable to that of the reference product. Both mAbs had highly similar neutralizing efficacy in HUVEC cell cultures stimulated with TNF-α. In vitro induction of CDC and ADCC were also similar between the evaluated products. In vivo comparability was assessed using a transgenic mouse model of arthritis that expresses human TNF-α in a 13-week multiple-administration study. Infliximab and infliximab-Probiomed showed comparable efficacy, safety, and pharmacokinetic profiles. Our results indicate that infliximab-Probiomed has highly similar activities to infliximab in preclinical models, warranting a clinical evaluation of its biosimilarity.
authors.affiliation: Facultad de Medicina, Universidad Nacional Autónoma de México, Cd. Universitaria, Cd. Mx. 04510, México.
authors.forename: M A
authors.initials: MA
authors.lastname: Velasco-Velázquez
authors.affiliation: Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, IPN. Prolongación de Carpio y Plan de Ayala s/n, Col. Sto. Tomás, Cd. Mx. 11340, México.
authors.forename: N
authors.initials: N
authors.lastname: Salinas-Jazmín
authors.affiliation: Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, IPN. Prolongación de Carpio y Plan de Ayala s/n, Col. Sto. Tomás, Cd. Mx. 11340, México.
authors.forename: E
authors.initials: E
authors.lastname: Hisaki-Itaya
authors.affiliation: Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, IPN. Prolongación de Carpio y Plan de Ayala s/n, Col. Sto. Tomás, Cd. Mx. 11340, México.
authors.forename: L
authors.initials: L
authors.lastname: Cobos-Puc
authors.affiliation: Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, IPN. Prolongación de Carpio y Plan de Ayala s/n, Col. Sto. Tomás, Cd. Mx. 11340, México.
authors.forename: W
authors.initials: W
authors.lastname: Xolalpa
authors.affiliation: Unidad de Desarrollo e Investigación, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, México.
authors.forename: G
authors.initials: G
authors.lastname: González
authors.affiliation: Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, IPN. Prolongación de Carpio y Plan de Ayala s/n, Col. Sto. Tomás, Cd. Mx. 11340, México.
authors.forename: A
authors.initials: A
authors.lastname: Tenorio-Calvo
authors.affiliation: Unidad de Desarrollo e Investigación, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, México.
authors.forename: N
authors.initials: N
authors.lastname: Piña-Lara
authors.affiliation: Unidad de Desarrollo e Investigación, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, México.
authors.forename: L C
authors.initials: LC
authors.lastname: Juárez-Bayardo
authors.affiliation: Unidad de Desarrollo e Investigación, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, México.
authors.forename: L F
authors.initials: LF
authors.lastname: Flores-Ortiz
authors.affiliation: Unidad de Desarrollo e Investigación, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, México.
authors.forename: E
authors.initials: E
authors.lastname: Medina-Rivero
authors.affiliation: Unidad de Desarrollo e Investigación, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, México. Electronic address: nestor.perez@probiomed.com.mx.
authors.forename: N O
authors.initials: NO
authors.lastname: Pérez
authors.affiliation: Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, IPN. Prolongación de Carpio y Plan de Ayala s/n, Col. Sto. Tomás, Cd. Mx. 11340, México; Departamento de Inmunología and Unidad de Investigación Desarrollo e Innovación Médica y Biotecnológica (UDIMEB), Escuela Nacional de Ciencias Biológicas, IPN, México. Electronic address: smpt.2011@hotmail.com.
authors.forename: S M
authors.initials: SM
authors.lastname: Pérez-Tapia
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy / Q000378:metabolism; D059451:Biosimilar Pharmaceuticals / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016466:CHO Cells; D002478:Cells, Cultured; D003412:Cricetulus; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000069285:Infliximab / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; D059451:Biosimilar Pharmaceuticals; D016207:Cytokines; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000069285:Infliximab
keywords: Biosimilar; Infliximab; Rheumatoid arthritis; TNF-α; Therapeutic mAb; anti-TNF-α