In this review, Sonia Guedan, Marco Ruella, and Carl June discuss recent advancements, current research, and future challenges in the field of adoptive T cell therapy. Remarkable clinical results have been observed in some patients with liquid tumors following adoptive transfer of expanded TILs, TCR-engineered T cells, or CAR-engineered T cells, but improving durable response rates, reducing toxicity, targeting solid tumors, and increasing patient access to cellular therapies remain key goals.

Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimeric antigen receptor (CAR) T cells were recently approved by the US Food and Drug Administration and are poised to enter the practice of medicine for leukemia and lymphoma, demonstrating that engineered immune cells can serve as a powerful new class of cancer therapeutics. The emergence of synthetic biology approaches for cellular engineering provides a broadly expanded set of tools for programming immune cells for enhanced function. Advances in T cell engineering, genetic editing, the selection of optimal lymphocytes, and cell manufacturing have the potential to broaden T cell-based therapies and foster new applications beyond oncology, in infectious diseases, organ transplantation, and autoimmunity. Expected final online publication date for the Annual Review of Immunology Volume 37 is April 26, 2019. Please see http://www.annualreviews.org/p... for revised estimates.

Author Info: (1) Department of Hematology, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; email: sguedan@clinic.cat. Center for Cellular Immunotherapies, Perelman School

Author Info: (1) Department of Hematology, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; email: sguedan@clinic.cat. Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email: cjune@upenn.edu. (2) Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email: cjune@upenn.edu. Department of Medicine, Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA. Parker Institute for Cellular Immunotherapy at the University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA. (3) Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email: cjune@upenn.edu. Department of Medicine, Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA. Parker Institute for Cellular Immunotherapy at the University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA. Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

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