title: T cells expressing a LMP1-specific chimeric antigen receptor mediate antitumor effects against LMP1-positive nasopharyngeal carcinoma cells in vitro and in vivo.
abstract: T cells modified with chimeric antigen receptor are an attractive strategy to treat Epstein-Barr virus (EBV) associated malignancies. The EBV latent membrane protein 1 (LMP1) is a 66-KD integral membrane protein encoded by EBV that consists of transmembrane-spanning loops. Previously, we have identified a functional signal chain variable fragment (scFv) that specifically recognizes LMP1 through phage library screening. Here, we constructed a LMP1 specific chimeric antigen receptor containing anti-LMP1 scFv, the CD28 signalling domain, and the CD3ζ chain (HELA/CAR). We tested its functional ability to target LMP1 positive nasopharyngeal carcinoma cells. HELA/CAR cells were efficiently generated using lentivirus vector encoding the LMP1-specific chimeric antigen receptor to infect activated human CD3+ T cells. The HELA/CAR T cells displayed LMP1 specific cytolytic action and produced IFN-γ and IL-2 in response to nasopharyngeal carcinoma cells overexpressing LMP1. To demonstrate in vivo anti-tumor activity, we tested the HELA/CAR T cells in a xenograft model using an LMP1 overexpressing tumor. Intratumoral injection of anti-LMP1 HELA/CAR-T cells significantly reduced tumor growth in vivo. These results show that targeting LMP1 using HELA/CAR cells could represent an alternative therapeutic approach for patients with EBV-positive cancers.
authors.affiliation: Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, China. ; The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Oncology, Ao Yang Hospital, Zhangjiagang, Jiangsu 215617, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Otolaryngological, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Li
authors.affiliation: The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Otolaryngological, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, China.
authors.forename: Renjie
authors.initials: R
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, Jiangsu 210029, China. ; Huadong Medical Institute of Biotechniques, Nanjing, Jiangsu 210002, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, China. ; The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, Jiangsu 210029, China. ; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Feng
keywords: EBV; LMP1; adoptive T cell therapy; chimeric antigen receptor; nasopharyngeal carcinoma