RESUMO
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.
Assuntos
Antirreumáticos , Medicamentos Biossimilares , Infliximab , Animais , Antirreumáticos/farmacocinética , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite/tratamento farmacológico , Artrite/metabolismo , Medicamentos Biossimilares/farmacocinética , Medicamentos Biossimilares/farmacologia , Medicamentos Biossimilares/uso terapêutico , Células CHO , Células Cultivadas , Cricetulus , Citocinas/genética , Citocinas/metabolismo , Selectina E/metabolismo , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Infliximab/farmacocinética , Infliximab/farmacologia , Infliximab/uso terapêutico , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
The first evidence of the interaction of Mycobacterium tuberculosis with the plasminogen system is herein reported. By FACScan analysis and affinity blotting, lysine-dependent binding of plasminogen to M. tuberculosis was demonstrated. The binding molecules were 30-, 60-, and 66-kDa proteins present in cell wall and soluble protein extracts. The activation of plasminogen, which occurred only in presence of fibrin and was not inhibited by the host serpin, alpha(2)-antiplasmin, was also demonstrated.
