title: Phase I trial of adoptively transferred tumor-infiltrating lymphocyte immunotherapy following concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.affiliation: 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 ;
authors.forename: Qiu-Yan
authors.initials: QY
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Jia
authors.initials: J
authors.lastname: He
authors.affiliation: 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.
authors.forename: Ze-Lei
authors.initials: ZL
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Tang
authors.affiliation: 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.
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Chuan-Miao
authors.initials: CM
authors.lastname: Xie
authors.affiliation: 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.
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Li-Xi
authors.initials: LX
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Shu-Bio
authors.initials: SB
authors.lastname: Ye
authors.affiliation: 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.
authors.forename: Miao-La
authors.initials: M
authors.lastname: Ke
authors.affiliation: 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 ;
authors.forename: Lin-Quan
authors.initials: LQ
authors.lastname: Tang
authors.affiliation: 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 ;
authors.forename: Huai
authors.initials: H
authors.lastname: Liu
authors.affiliation: 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 ;
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 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 ;
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Jian-Chuan
authors.initials: JC
authors.lastname: Xia
authors.affiliation: 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.
authors.forename: Xiao-Shi
authors.initials: XS
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Zheng
authors.affiliation: 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 ;
authors.forename: Xiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: 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 ;
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
authors.affiliation: 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 ;
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Mai
authors.affiliation: 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.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
keywords: ACT, adoptive cell therapy; CCRT, concurrent chemoradiotherapy; CR, complete response; DFS, disease-free survival, EBNA1; EBV, Epstein–Barr virus; EBV-CTLs, EBV-specific cytotoxic T cells; ELISPOT, enzyme-linked immunospot; Epstein–Barr virus nuclear antigen 1; FACS, fluorescence-activated cell sorting; GMP, good manufacturing practices; LMP1, latent membrane protein-1; LMP2, latent membrane protein-2; NPC, nasopharyngeal carcinoma; PBMCs, peripheral blood mononuclear cells; PD, progressive disease; PR, partial response; REP, rapid expansion protocol; SFCs, spot-forming cells; TILs, tumor-infiltrating lymphocytes; adoptive cell therapy; nasopharyngeal carcinoma; tumor-infiltrating lymphocytes