https://scholars.lib.ntu.edu.tw/handle/123456789/640188
標題: | Sequential Therapy with Ropeginterferon Alfa-2b and Anti-Programmed Cell Death 1 Antibody for Inhibiting the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma: From Animal Modeling to Phase I Clinical Results | 作者: | Qin, Albert Wu, Chang-Ru MING-CHIH HO Tsai, Chan-Yen PEI-JER CHEN |
關鍵字: | HBV-related; animal HBV model; anti-PD1 antibody; clinical trial; hepatocellular carcinoma; ropeginterferon alfa-2b | 公開日期: | 一月-2024 | 卷: | 25 | 期: | 1 | 起(迄)頁: | 433 | 來源出版物: | International journal of molecular sciences | 摘要: | Hepatocellular carcinoma (HCC) usually recurs after curative surgical resection. Currently, no approved adjuvant therapy has been shown to reduce HCC recurrence rates. In this study, the in vivo effect of sequential combination treatment with recombinant mouse interferon-alpha (rmIFN-α) and an anti-mouse-PD1 antibody on hepatitis B virus (HBV) clearance in mice was evaluated. A Phase I clinical trial was then conducted to assess the safety, tolerability, and inhibitory activity of sequential therapy with ropeginterferon alfa-2b and nivolumab in patients with HCC recurrence who underwent curative surgery for HBV-related HCC. The animal modeling study showed that HBV suppression was significantly greater with the rmIFN-α and anti-PD1 sequential combination treatment in comparison with sole treatment with rmIFN-α or anti-PD1. In the Phase I study, eleven patients completed the sequential therapy with ropeginterferon alfa-2b every two weeks for six doses at 450 µg, followed by three doses of nivolumab every two weeks up to 0.75 mg/kg. A notable decrease in or clearance of HBV surface antigen was observed in two patients. The dose-limiting toxicity of grade 3 alanine transaminase and aspartate aminotransferase increases was observed in one patient. The maximum tolerated dose was then determined. To date, no HCC recurrence has been observed. The treatment modality was well tolerated. These data support the further clinical development of sequential combination therapy as a post-surgery prophylactic measure against the recurrence of HBV-related HCC. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/640188 | ISSN: | 16616596 | DOI: | 10.3390/ijms25010433 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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