PMID- 25949875 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210112 IS - 2162-4011 (Print) IS - 2162-402X (Electronic) IS - 2162-4011 (Linking) VI - 4 IP - 2 DP - 2015 Feb TI - Phase I trial of adoptively transferred tumor-infiltrating lymphocyte immunotherapy following concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. PG - e976507 LID - e976507 AB - Adoptive cell therapy (ACT) for cancers using autologous tumor-infiltrating lymphocytes (TILs) can induce immune responses and antitumor activity in metastatic melanoma patients. Here, we aimed to assess the safety and antitumor activity of ACT using expanded TILs following concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Twenty-three newly diagnosed, locoregionally advanced NPC patients were enrolled, of whom 20 received a single-dose of TIL infusion following CCRT. All treated patients were assessed for toxicity, survival and clinical and immunologic responses. Correlations between immunological responses and treatment effectiveness were further studied. Only mild adverse events (AEs), including Grade 3 neutropenia (1/23, 5%) consistent with immune-related causes, were observed. Nineteen of 20 patients exhibited an objective antitumor response, and 18 patients displayed disease-free survival longer than 12 mo after ACT. A measurable plasma Epstein-Barr virus (EBV) load was detected in 14 patients at diagnosis, but a measurable EBV load was not found in patients after one week of ACT, and the plasma EBV load remained undetectable in 17 patients at 6 mo after ACT. Expansion and persistence of T cells specific for EBV antigens in peripheral blood following TIL therapy were observed in 13 patients. The apparent positive correlation between tumor regression and the expansion of T cells specific for EBV was further investigated in four patients. This study shows that NPC patients can tolerate ACT with TILs following CCRT and that this treatment results in sustained antitumor activity and anti-EBV immune responses. A larger phase II trial is in progress. FAU - Li, Jiang AU - Li J AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Biotherapy; Sun Yat-sen University Cancer Center ; Guangzhou, China. FAU - Chen, Qiu-Yan AU - Chen QY AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Nasopharyngeal Carcinoma ; FAU - He, Jia AU - He J AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Biotherapy; Sun Yat-sen University Cancer Center ; Guangzhou, China. FAU - Li, Ze-Lei AU - Li ZL AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Biotherapy; Sun Yat-sen University Cancer Center ; Guangzhou, China. FAU - Tang, Xiao-Feng AU - Tang XF AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Biotherapy; Sun Yat-sen University Cancer Center ; Guangzhou, China. FAU - Chen, Shi-Ping AU - Chen SP AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Biotherapy; Sun Yat-sen University Cancer Center ; Guangzhou, China. FAU - Xie, Chuan-Miao AU - Xie CM AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Imaging Diagnostic and Interventional Center; Sun Yat-sen University Cancer Center ; Guangzhou, China. FAU - Li, Yong-Qiang AU - Li YQ AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Biotherapy; Sun Yat-sen University Cancer Center ; Guangzhou, China. FAU - Huang, Li-Xi AU - Huang LX AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Biotherapy; Sun Yat-sen University Cancer Center ; Guangzhou, China. FAU - Ye, Shu-Bio AU - Ye SB AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Biotherapy; Sun Yat-sen University Cancer Center ; Guangzhou, China. FAU - Ke, Miao-La AU - Ke M AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Biotherapy; Sun Yat-sen University Cancer Center ; Guangzhou, China. FAU - Tang, Lin-Quan AU - Tang LQ AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Nasopharyngeal Carcinoma ; FAU - Liu, Huai AU - Liu H AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Nasopharyngeal Carcinoma ; FAU - Zhang, Lu AU - Zhang L AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Nasopharyngeal Carcinoma ; FAU - Guo, Shan-Shan AU - Guo SS AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Nasopharyngeal Carcinoma ; FAU - Xia, Jian-Chuan AU - Xia JC AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Biotherapy; Sun Yat-sen University Cancer Center ; Guangzhou, China. FAU - Zhang, Xiao-Shi AU - Zhang XS AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Biotherapy; Sun Yat-sen University Cancer Center ; Guangzhou, China. FAU - Zheng, Li-Min AU - Zheng LM AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Biotherapy; Sun Yat-sen University Cancer Center ; Guangzhou, China. FAU - Guo, Xiang AU - Guo X AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Nasopharyngeal Carcinoma ; FAU - Qian, Chao-Nan AU - Qian CN AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Nasopharyngeal Carcinoma ; FAU - Mai, Hai-Qiang AU - Mai HQ AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Department of Nasopharyngeal Carcinoma ; FAU - Zeng, Yi-Xin AU - Zeng YX AD - State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center ; Guangzhou, China ; Collaborative Innovation Center of Cancer Medicine; Sun Yat-sen University Cancer Center ; Guangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150306 PL - United States TA - Oncoimmunology JT - Oncoimmunology JID - 101570526 PMC - PMC4404907 OTO - NOTNLM OT - ACT, adoptive cell therapy OT - CCRT, concurrent chemoradiotherapy OT - CR, complete response OT - DFS, disease-free survival, EBNA1 OT - EBV, Epstein-Barr virus OT - EBV-CTLs, EBV-specific cytotoxic T cells OT - ELISPOT, enzyme-linked immunospot OT - Epstein-Barr virus nuclear antigen 1 OT - FACS, fluorescence-activated cell sorting OT - GMP, good manufacturing practices OT - LMP1, latent membrane protein-1 OT - LMP2, latent membrane protein-2 OT - NPC, nasopharyngeal carcinoma OT - PBMCs, peripheral blood mononuclear cells OT - PD, progressive disease OT - PR, partial response OT - REP, rapid expansion protocol OT - SFCs, spot-forming cells OT - TILs, tumor-infiltrating lymphocytes OT - adoptive cell therapy OT - nasopharyngeal carcinoma OT - tumor-infiltrating lymphocytes EDAT- 2015/05/08 06:00 MHDA- 2015/05/08 06:01 PMCR- 2016/03/06 CRDT- 2015/05/08 06:00 PHST- 2014/08/07 00:00 [received] PHST- 2014/10/10 00:00 [accepted] PHST- 2015/05/08 06:00 [entrez] PHST- 2015/05/08 06:00 [pubmed] PHST- 2015/05/08 06:01 [medline] PHST- 2016/03/06 00:00 [pmc-release] AID - 976507 [pii] AID - 10.4161/23723556.2014.976507 [doi] PST - epublish SO - Oncoimmunology. 2015 Mar 6;4(2):e976507. doi: 10.4161/23723556.2014.976507. eCollection 2015 Feb.