title: Genetically Modified T-Cell-Based Adoptive Immunotherapy in Hematological Malignancies.
abstract: A significant proportion of hematological malignancies remain limited in treatment options. Immune system modulation serves as a promising therapeutic approach to eliminate malignant cells. Cytotoxic T lymphocytes (CTLs) play a central role in antitumor immunity; unfortunately, nonspecific approaches for targeted recognition of tumor cells by CTLs to mediate tumor immune evasion in hematological malignancies imply multiple mechanisms, which may or may not be clinically relevant. Recently, genetically modified T-cell-based adoptive immunotherapy approaches, including chimeric antigen receptor (CAR) T-cell therapy and engineered T-cell receptor (TCR) T-cell therapy, promise to overcome immune evasion by redirecting the specificity of CTLs to tumor cells. In clinic trials, CAR-T-cell- and TCR-T-cell-based adoptive immunotherapy have produced encouraging clinical outcomes, thereby demonstrating their therapeutic potential in mitigating tumor development. The purpose of the present review is to (1) provide a detailed overview of the multiple mechanisms for immune evasion related with T-cell-based therapies; (2) provide a current summary of the applications of CAR-T-cell- as well as neoantigen-specific TCR-T-cell-based adoptive immunotherapy and routes taken to overcome immune evasion; and (3) evaluate alternative approaches targeting immune evasionviaoptimization of CAR-T and TCR-T-cell immunotherapies.
authors.affiliation: Department of Hematology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
authors.forename: Baixin
authors.initials: B
authors.lastname: Ye
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305-5117, USA.
authors.forename: Creed M
authors.identifier: 0000-0001-9876-6634
authors.initials: CM
authors.lastname: Stary
authors.affiliation: Department of Hematology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Hematology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
authors.forename: Qiongyu
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
authors.forename: Zhihong
authors.identifier: 0000-0002-9150-5789
authors.initials: Z
authors.lastname: Jian
authors.affiliation: Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
authors.forename: Lijuan
authors.identifier: 0000-0003-1928-8772
authors.initials: L
authors.lastname: Gu
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
authors.forename: Xiaoxing
authors.identifier: 0000-0001-6983-8547
authors.initials: X
authors.lastname: Xiong
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D015316:Genetic Therapy; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation*; D019139:Tumor Escape
chemical_list: D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins