Clinical Trials Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2017; 23(29): 5395-5404
Published online Aug 7, 2017. doi: 10.3748/wjg.v23.i29.5395
Phase I clinical study of personalized peptide vaccination combined with radiotherapy for advanced hepatocellular carcinoma
Jie Shen, Li-Feng Wang, Zheng-Yun Zou, Wei-Wei Kong, Jing Yan, Fan-Yan Meng, Fang-Jun Chen, Juan Du, Jie Shao, Qiu-Ping Xu, Hao-Zhen Ren, Ru-Tian Li, Jia Wei, Xiao-Ping Qian, Bao-Rui Liu
Jie Shen, Li-Feng Wang, Zheng-Yun Zou, Wei-Wei Kong, Jing Yan, Fan-Yan Meng, Fang-Jun Chen, Juan Du, Jie Shao, Qiu-Ping Xu, Ru-Tian Li, Jia Wei, Xiao-Ping Qian, Bao-Rui Liu, Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing 210008, Jiangsu Province, China
Hao-Zhen Ren, Department of Hepatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing Universit-y, Nanjing 210008, Jiangsu Province, China
Author contributions: Shen J, Wang LF and Zou ZY contributed equally to this work; Shen J, Liu BR, Wang LF and Chen FJ were responsible for the study design and experiment adjustments; Shen J, Zou ZY, Du J, Xu QP and Meng FY performed the experiments, drafted the manuscript and conducted the statistical analysis; Li RT, Wang LF, Qian XP and Wei J collected the blood samples and clinical information of patients; All authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81401969; Jiangsu Provincial Medical Youth Talent, No. QNRC2016043; and the Key Medical Science and Technology Development Project of Nanjing, No. ZKX16032.
Institutional review board statement: The study was reviewed and approved by the ethical review board of Comprehensive Cancer Centre of Drum Tower Hospital and by the Drum Tower Hospital ethical review board.
Clinical trial registration statement: This study was registered at http://www.chictr.org.cn/edit.aspx?pid=16964&htm=4. The registration identification number is ChiCTR-OIC-16010025.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: None declared.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Bao-Rui Liu, MD, PhD, Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu Province, China. baoruiliu@nju.edu.cn
Telephone: +86-25-83106666-61331 Fax: +86-25-83105082
Received: January 15, 2016
Peer-review started: January 16, 2016
First decision: February 9, 2017
Revised: February 25, 2017
Accepted: March 4, 2017
Article in press: March 6, 2017
Published online: August 7, 2017
Processing time: 203 Days and 10.7 Hours
Abstract
AIM

To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination (PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma (HCC).

METHODS

A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases (the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL.

RESULTS

Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response (PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade II bone marrow suppression and the remaining patients had no significant hematological side effects.

CONCLUSION

Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.

Keywords: Personalized peptide vaccination; TOMO radiotherapy; Cytotoxic lymphocytes; Hepatocellular carcinoma

Core tip: Advanced hepatocellular carcinoma (HCC) is a challenging disease to treat because of its advanced stage at diagnosis and rapid progression. We developed a new treatment modality, cellular immune therapy based on personalized peptide vaccination combined with radiotherapy, to treat advanced HCC. It integrates personalized peptide vaccination in tumor immunotherapy, takes full advantages of the immune modulation of radiotherapy, promotes tumor cells to release antigens and results in a more effective therapeutic strategy with regard to local and systemic control.