Physicochemical and functional characterization of trastuzumab-dkst, a trastuzumab biosimilar.
Future Med Chem
; 13(18): 1531-1557, 2021 09.
Article
en En
| MEDLINE
| ID: mdl-34289749
ABSTRACT
Aims:
Preclinical comparative similarity studies of trastuzumab-dkst, a Herceptin® biosimilar, are reported. Materials &methods:
Primary sequence and higher order structure and pharmacological mechanisms of action were compared using multiple techniques. Pharmacokinetics and repeat-dose toxicity were assessed in cynomolgus monkeys.Results:
Primary structures were identical; secondary and tertiary structures were highly similar. Non-significant differences were observed for charge heterogeneity. Twelve of 13 glycan species were highly similar, with slightly higher total mannose levels in trastuzumab-dkst. FcγR and FcRn binding activity was highly similar. Each drug equally inhibited HER2+ cell proliferation, demonstrating equivalent relative potency in mediating HER2+ cell cytolysis by antibody-dependent cellular cytotoxicity. Pharmacokinetic and toxicological profiles in cynomolgus monkeys were similar.Conclusion:
Trastuzumab-dkst, US-licensed trastuzumab and EU-approved trastuzumab demonstrate high structural and functional similarity.Palabras clave
Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Polisacáridos
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Neoplasias de la Mama
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Biosimilares Farmacéuticos
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Trastuzumab
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Antineoplásicos Inmunológicos
Idioma:
En
Revista:
Future Med Chem
Año:
2021
Tipo del documento:
Article