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.
MeSH terms
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Antigen Presentation
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Antigens, CD19 / immunology
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Antigens, Neoplasm / immunology
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Clinical Trials as Topic
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Costimulatory and Inhibitory T-Cell Receptors / genetics
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Costimulatory and Inhibitory T-Cell Receptors / immunology
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Cytokines / metabolism
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Forecasting
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Gene Editing
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Gene Transfer Techniques
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Genetic Engineering
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HLA Antigens / immunology
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Hematologic Neoplasms / immunology
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Hematologic Neoplasms / therapy
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Humans
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Immunotherapy, Adoptive / adverse effects
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Immunotherapy, Adoptive / methods*
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Immunotherapy, Adoptive / trends
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Models, Immunological
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Neoplasms / immunology
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Neoplasms / therapy*
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Syndrome
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T-Cell Antigen Receptor Specificity
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / transplantation
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Tumor Escape
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Tumor Microenvironment / immunology
Substances
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Antigens, CD19
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Antigens, Neoplasm
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CD19 molecule, human
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Costimulatory and Inhibitory T-Cell Receptors
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Cytokines
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HLA Antigens
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Receptors, Antigen, T-Cell
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Recombinant Fusion Proteins