@article{0deb6c7ef733473eaccdeab169c92e9e,
title = "Virus-specific T cells engineered to coexpress tumor-specific receptors: Persistence and antitumor activity in individuals with neuroblastoma",
abstract = "Cytotoxic T lymphocytes (CTLs) directed to nonviral tumor-associated antigens do not survive long term and have limited antitumor activity in vivo, in part because such tumor cells typically lack the appropriate costimulatory molecules. We therefore engineered Epstein-Barr virus (EBV)-specific CTLs to express a chimeric antigen receptor directed to the diasialoganglioside GD2, a nonviral tumor-associated antigen expressed by human neuroblastoma cells. We reasoned that these genetically engineered lymphocytes would receive optimal costimulation after engagement of their native receptors, enhancing survival and antitumor activity mediated through their chimeric receptors. Here we show in individuals with neuroblastoma that EBV-specific CTLs expressing a chimeric GD2-specific receptor indeed survive longer than T cells activated by the CD3-specific antibody OKT3 and expressing the same chimeric receptor but lacking virus specificity. Infusion of these genetically modified cells seemed safe and was associated with tumor regression or necrosis in half of the subjects tested. Hence, virus-specific CTLs can be modified to function as tumor-directed effector cells.",
author = "Pule, {Martin A.} and Barbara Savoldo and Myers, {G. Doug} and Claudia Rossig and Russell, {Heidi V.} and Gianpietro Dotti and Huls, {M. Helen} and Enli Liu and Gee, {Adrian P.} and Zhuyong Mei and Eric Yvon and Weiss, {Heidi L.} and Hao Liu and Rooney, {Cliona M.} and Helen Heslop and Malcolm Brenner",
note = "Funding Information: Author Affiliations: Division of General Internal Medicine (JMZ), Department of Medicine (CJ), and Center for Health Systems Effectiveness (KJM), Oregon Health & Science University, Portland, OR; Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health (DP), Baltimore, MD. Source of Funding: This work was supported by the National Institutes of Mental Health (1K08MH123624-01). Author Disclosures: Dr Zhu has received consultant fees from Omada Health and grants from NIHCM Foundation on topics unrelated to this study. The remaining authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article. Authorship Information: Concept and design (JMZ, CJ, KJM); acquisition of data (JMZ, CJ); analysis and interpretation of data (JMZ, DP, CJ); drafting of the manuscript (JMZ, DP, CJ); critical revision of the manuscript for important intellectual content (JMZ, DP, KJM); statistical analysis (JMZ); obtaining funding (JMZ); administrative, technical, or logistic support (JMZ, KJM); and supervision (JMZ, DP, KJM). Address Correspondence to: Jane M. Zhu, MD, MPP, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239. Email: zhujan@ohsu.edu.",
year = "2008",
month = nov,
doi = "10.1038/nm.1882",
language = "English (US)",
volume = "14",
pages = "1264--1270",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "11",
}