Study Of A Panitumumab Biosimilar On Tumor Inhibition And Radiosensitivity

ObjectiveCompare the similarity of the biological activity and tumor inhibition between a Panitumumab biosimilar KN032 and Panitumumab, and study radiosensitivity and the mechanism of this biosimilar.MethodChoose the EGFR high expression cell line A431 as research object. Use MTT experiment to measure the tumor inhibition of KN032 and Panitumumab in vitro, and compare the biological activity similarity of tumor inhibition between them. Use flow cytometry to measure the ability of Panitumumab and KN032 to bind to A431, and compare their similarity. In vivo effect on the growth of A431 xenografts was assessed in athymic nude mice. The effect on radiosensitivity was measured by clonogenic survival assay. Immunofluorescence method was used to assess the expression of γ-H2 AX in different treatment groups: RT、RT+KN032 and RT+Panitumumab.ResultsMTT results show that Panitumumab and KN032 can inhibit growth of A431, and the higher of drug concentration, the stronger ability to inhibit tumor growth under 4μg/mL. In the same concentration, the ability of them were similarity. EC50 of KN032 is 0.21, and EC50 of Panitumumab is 0.23. The flow cytometry outcomes show that the ability of KN032 to blind to A431 is similar as Panitumumab. In vivo, both of KN032 and Panitumumab can inhibit the mice tumor growth, and the effect is stronger in dose 200μg than in dose 20μg, but in the same dose, the effect of these two drugs were similar. The clonogenic survival assay show that KN032 and Panitumumab own the similar ability of radiosensitivity. Either KN032 or Panitumumab combined with radiation had significant increased to expression of γ-H2 AX by Immunofluorescence method after 0.5 or 4h ofradiation(P<0.05). At the time after 12 h of radiation, the expression of γ-H2 AX in control、KN032 and Panitumumab group were similar, no obvious difference between them.ConclusionKN032 can effectively inhibit the tumor growth and its biological was similar as Panitumumab. KN032 can improve the ability of radiosensitivity, and its mechanism may be related with significant enhancement of DNA injury.