A phase I clinical trial utilizing autologous tumor-infiltrating lymphocytes in patients with primary hepatocellular carcinoma

Abstract

// Shan-Shan Jiang 1, * , Yan Tang 1, * , Yao-Jun Zhang 2, * , De-Sheng Weng 1 , Zhong-Guo Zhou 2 , Ke Pan 1 , Qiu-Zhong Pan 1 , Qi-Jing Wang 1 , Qing Liu 1 , Jia He 1 , Jing-Jing Zhao 1 , Jiang Li 1 , Min-Shan Chen 2 , Alfred E. Chang 3 , Qiao Li 3 , Jian-Chuan Xia 1 1 Department of Biotherapy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China 2 Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China 3 University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA * These authors have contributed equally to this work Correspondence to: Jian-Chuan Xia, e-mail: xiajch@mail.sysu.edu.cn Qiao Li, e-mail: qiaoli@umich.edu Keywords: primary hepatocellular carcinoma, autologous tumor-infiltrating lymphocytes, adoptive cell therapy Received: July 15, 2015      Accepted: September 01, 2015      Published: October 20, 2015 ABSTRACT This report describes an ongoing Phase I clinical trial testing the safety of adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) in patients with primary hepatocellular carcinoma (HCC). Fifteen HCC patients were treated with their activated and expanded TILs following tumor resection. From a total of 17 patients with HCC, TIL were successfully expanded from 15 patients (88%), whereas two patients showed minimal or no expansion of TIL. Transient increase in the frequency of T cells was observed after adoptive transfer who was found only associated with grade I flu-like symptoms and malaise. After a median follow-up of 14 months, 15 patients (100%) were alive; and 12 patients (80%) showed no evidence of disease, 3 patients (patient 1,11,12) had tumor recurrence. The time to the diagnosis of tumor recurrence following therapy ranged from 105 to 261 days. These results indicate that immunotherapy with activated and expanded autologous TIL could be successfully performed with low toxicity, thus would serve as a novel treatment modality for patients with HCC.