title: Improving the efficacy and safety of engineered T cell therapy for cancer.
abstract: Adoptive T-cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) is a powerful immunotherapeutics approach against metastatic melanoma. The success of TIL therapy has led to novel strategies for redirecting normal T cells to recognize tumor-associated antigens (TAAs) by genetically engineering tumor antigen-specific T cell receptors (TCRs) or chimeric antigen receptor (CAR) genes. In this manner, large numbers of antigen-specific T cells can be rapidly generated compared with the longer term expansion of TILs. Great efforts have been made to improve these approaches. Initial clinical studies have demonstrated that genetically engineered T cells can mediate tumor regression in vivo. In this review, we discuss the development of TCR and CAR gene-engineered T cells and the safety concerns surrounding the use of these T cells in patients. We highlight the importance of judicious selection of TAAs for modified T cell therapy and propose solutions for potential "on-target, off-organ" toxicity.
authors.affiliation: Department of Oncology, Shandong Cancer Hospital and Institute, No. 440 Jiyan Road, Jinan, Shandong 250117, PR China.
authors.forename: Huan
authors.initials: H
authors.lastname: Shi
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Zhehai
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D011946:Receptors, Antigen / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D011946:Receptors, Antigen; D011948:Receptors, Antigen, T-Cell