Establishment and Preclinical Therapy of Patient-derived Hepatocellular Carcinoma Xenograft Model

Yuwei Wu; Jinyu Wang; Xiaodong Zheng; Yongyan Chen; Mei Huang; Qiang Huang; Weihua Xiao; Haiming Wei; Zhigang Tian; Rui Sun; Cheng Sun

doi:10.1016/j.imlet.2020.04.009

Establishment and Preclinical Therapy of Patient-derived Hepatocellular Carcinoma Xenograft Model

Immunol Lett. 2020 Jul:223:33-43. doi: 10.1016/j.imlet.2020.04.009. Epub 2020 Apr 23.

Authors

Yuwei Wu¹, Jinyu Wang¹, Xiaodong Zheng¹, Yongyan Chen¹, Mei Huang², Qiang Huang³, Weihua Xiao¹, Haiming Wei¹, Zhigang Tian¹, Rui Sun⁴, Cheng Sun⁵

Affiliations

¹ Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, China; Institute of Immunology, University of Science and Technology of China, China.
² Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, China.
³ Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of University of Science & Technology of China, Hefei, China.
⁴ Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, China; Institute of Immunology, University of Science and Technology of China, China. Electronic address: sunr@ustc.edu.cn.
⁵ Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, China; Institute of Immunology, University of Science and Technology of China, China; Transplant & Immunology Laboratory, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui, China. Electronic address: charless@ustc.edu.cn.

PMID: 32335145
DOI: 10.1016/j.imlet.2020.04.009

Abstract

Hepatocellular carcinoma (HCC) is a world-wide health problem. Poor and delayed diagnoses as well as high recurrence rate resulting in high mortality rate. In this study, we established a patient-derived xenograft (PDX) model from HCC patient, and continuously maintained with subcutaneous passage more than 20 times. This HCC PDX tumor exhibited the same histological characteristics with the HCC patient and could be used to verify therapeutic effect of liver cancer. We further evaluated this PDX model by experimental chemotherapy, demonstrating that this HCC PDX model was sensitive to sorafenib treatment. Further, the potential of natural killer cell-based immunotherapy for HCC was tested using this model. We found that NK92 cells effectively suppressed the tumor growth in vivo and prolonged the survival time of HCC-bearing PDX mice. This study indicates that HCC PDX model is a good platform to testify the efficacy of preclinical chemotherapy and immunotherapy.

Keywords: Hepatocellular carcinoma; Immunotherapy; NK cell; Patient-derived xenograft.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / therapeutic use*
Carcinoma, Hepatocellular / drug therapy
Carcinoma, Hepatocellular / pathology*
Cell Line, Tumor
Disease Models, Animal
Drug Evaluation, Preclinical
Heterografts
Humans
Immunotherapy / methods*
Killer Cells, Natural / immunology*
Liver Neoplasms / drug therapy
Liver Neoplasms / pathology*
Mice
Mice, SCID
Sorafenib / therapeutic use*
Xenograft Model Antitumor Assays / methods*

Substances

Antineoplastic Agents
Sorafenib