title: Engineered T cells: the promise and challenges of cancer immunotherapy.
abstract: The immune system evolved to distinguish non-self from self to protect the organism. As cancer is derived from our own cells, immune responses to dysregulated cell growth present a unique challenge. This is compounded by mechanisms of immune evasion and immunosuppression that develop in the tumour microenvironment. The modern genetic toolbox enables the adoptive transfer of engineered T cells to create enhanced anticancer immune functions where natural cancer-specific immune responses have failed. Genetically engineered T cells, so-called 'living drugs', represent a new paradigm in anticancer therapy. Recent clinical trials using T cells engineered to express chimeric antigen receptors (CARs) or engineered T cell receptors (TCRs) have produced stunning results in patients with relapsed or refractory haematological malignancies. In this Review we describe some of the most recent and promising advances in engineered T cell therapy with a particular emphasis on what the next generation of T cell therapy is likely to entail.
authors.affiliation: Department of Pathology and Laboratory Medicine and Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-5156, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Fesnak
authors.affiliation: Department of Pathology and Laboratory Medicine and Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-5156, USA.
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
authors.affiliation: Department of Pathology and Laboratory Medicine and Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-5156, USA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Levine
mesh_terms: D017951:Antigen Presentation; D018941:Antigens, CD19 / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D002986:Clinical Trials as Topic; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005544:Forecasting; D000072669:Gene Editing; D018014:Gene Transfer Techniques; D005818:Genetic Engineering; D006680:HLA Antigens / Q000276:immunology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods* / Q000639:trends; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013577:Syndrome; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D019139:Tumor Escape; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D018941:Antigens, CD19; D000951:Antigens, Neoplasm; C000604811:CD19 molecule, human; D061025:Costimulatory and Inhibitory T-Cell Receptors; D016207:Cytokines; D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins