Synergistic effect of OK-432 in combination with an anti-PD-1 antibody for residual tumors after radiofrequency ablation of hepatocellular carcinoma

Tao Sun; Bo Sun; Yanyan Cao; Jiayun Liu; Juan Chen; Bin Liang; Chuansheng Zheng; Xuefeng Kan

Biomedicine & Pharmacotherapy (Oct 2023)

Synergistic effect of OK-432 in combination with an anti-PD-1 antibody for residual tumors after radiofrequency ablation of hepatocellular carcinoma

Tao Sun,
Bo Sun,
Yanyan Cao,
Jiayun Liu,
Juan Chen,
Bin Liang,
Chuansheng Zheng,
Xuefeng Kan

Affiliations

Tao Sun: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
Bo Sun: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
Yanyan Cao: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
Jiayun Liu: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
Juan Chen: Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Bin Liang: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
Chuansheng Zheng: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China; Corresponding authors at: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Xuefeng Kan: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China; Corresponding authors at: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Journal volume & issue: Vol. 166
p. 115351

Abstract

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Background and aims: Radiofrequency ablation (RFA) often results in incomplete ablation for medium-to-large and irregular tumors. To solve this clinical problem, we proposed a new treatment strategy of OK-432 in combination with an anti-programmed cell death protein 1 (αPD-1) antibody for residual tumors after incomplete RFA (iRFA) of hepatocellular carcinoma (HCC). Approach and results: The effect of OK-432 on immature dendritic cells (iDCs) was evaluated in vitro. A CCK-8 kit and ELISPOT were used to assess the killing effect of OK-432-induced CD8+ T cells in combination with an αPD-1 antibody on Hepa1–6 cells. We found that OK-432 significantly increased the maturation level of DCs, and OK-432-induced CD8+ T cells in combination with αPD-1 antibody significantly enhanced the function of CD8+ T cells. In the in vivo experiment, HCC model mice were treated with (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + OK-432; (4) iRFA + αPD-1; or (5) iRFA + OK-432 + αPD-1. We found that the combined therapy of OK-432 with αPD-1 antibody significantly increased the infiltration and function of CD8+ T cells and significantly decreased the number of FoxP3+ regulatory T cells in residual tumors after iRFA of HCC. Moreover, the smallest tumor volumes and the longest survival were observed in the triple combination treatment (iRFA+OK-432 +αPD-1 antibody) group compared with the other four groups. Conclusions: The combined therapy of OK-432 with αPD-1 antibody induced a strong antitumor immune response, which significantly inhibited the residual tumors after iRFA of HCC. This concept may provide a new treatment strategy to increase the curative efficacy of RFA for medium-to-large and irregular HCCs. Availability of data and material: The data of this study are available from the corresponding author on reasonable request.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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