PreprintCommunicationVersion 3Preserved in Portico This version is not peer-reviewed
Sequential Therapy with Ropeginterferon Alfa-2b and Anti-PD1 Antibody for Inhibiting Recurrence of Hepatitis B-related Hepatocellular Carcinoma: From Animal Modeling to Phase I Clinical Results
Version 1
: Received: 6 December 2023 / Approved: 6 December 2023 / Online: 7 December 2023 (03:04:15 CET)
Version 2
: Received: 7 December 2023 / Approved: 7 December 2023 / Online: 8 December 2023 (02:53:09 CET)
Version 3
: Received: 8 December 2023 / Approved: 8 December 2023 / Online: 8 December 2023 (12:37:22 CET)
Qin, A.; Wu, C.-R.; Ho, M.-C.; Tsai, C.-Y.; Chen, P.-J. 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. Int. J. Mol. Sci.2024, 25, 433.
Qin, A.; Wu, C.-R.; Ho, M.-C.; Tsai, C.-Y.; Chen, P.-J. 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. Int. J. Mol. Sci. 2024, 25, 433.
Qin, A.; Wu, C.-R.; Ho, M.-C.; Tsai, C.-Y.; Chen, P.-J. 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. Int. J. Mol. Sci.2024, 25, 433.
Qin, A.; Wu, C.-R.; Ho, M.-C.; Tsai, C.-Y.; Chen, P.-J. 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. Int. J. Mol. Sci. 2024, 25, 433.
Abstract
In hepatocellular carcinoma (HCC), recurrence usually occurs after curative surgical resection. Currently, no approved adjuvant therapy has been shown to reduce recurrence rates. In this report, the in vivo mouse effect of sequential combination treatment with recombinant mouse interferon-alpha (rmIFN-α) and an anti-mouse-PD1 antibody on hepatitis B virus (HBV) clearance 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 HCC recurrence in patients who have undergone curative surgery for HBV-related HCC. In animal modeling, HBV suppression was significantly greater with rmIFN-α and anti-PD1 sequential combination treatment than with their treatment alone. In the Phase I study, eleven patients completed the sequential therapy with ropeginterferon alfa-2b every two weeks at the dose of 450 µg for six doses, followed by three doses of nivolumab every two weeks up to 0.75 mg/kg. A notable decrease or clearance of HBV surface antigen was observed in two patients. Dose-limiting toxicity of grade 3 alanine transaminase and aspartate aminotransferase increases was observed in one patient. The maximum tolerated dose was determined. Currently no HCC recurrence has been observed. The treatment modality was well tolerated. The data support further clinical development of sequential combination therapy as a post-surgery prophylactic measure against the recurrence of HBV-related HCC.
Medicine and Pharmacology, Medicine and Pharmacology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received:
8 December 2023
Commenter:
Albert Qin
Commenter's Conflict of Interests:
Author
Comment:
Dear Editors, We have now revised our manuscript to minimize self-citations according to your comments. Please kindly see the attachment below. Many thanks.
Commenter: Albert Qin
Commenter's Conflict of Interests: Author
We have now revised our manuscript to minimize self-citations according to your comments. Please kindly see the attachment below. Many thanks.