title: CAR T-cell immunotherapy: The path from the by-road to the freeway?
abstract: Chimeric antigen receptors are genetically encoded artificial fusion molecules that can re-program the specificity of peripheral blood polyclonal T-cells against a selected cell surface target. Unparallelled clinical efficacy has recently been demonstrated using this approach to treat patients with refractory B-cell malignancy. However, the approach is technically challenging and can elicit severe toxicity in patients. Moreover, solid tumours have largely proven refractory to this approach. In this review, we describe the important structural features of CARs and how this may influence function. Emerging clinical experience is summarized in both solid tumours and haematological malignancies. Finally, we consider the particular challenges imposed by solid tumours to the successful development of CAR T-cell immunotherapy, together with a number of innovative strategies that have been developed in an effort to reverse the balance in favour of therapeutic benefit.
authors.affiliation: King's College London, King's Health Partners Integrated Cancer Centre, Department of Research Oncology, Guy's Hospital Campus, Great Maze Pond, London SE1 9RT, UK. Electronic address: lynsey.whilding@kcl.ac.uk.
authors.forename: Lynsey M
authors.initials: LM
authors.lastname: Whilding
authors.affiliation: King's College London, King's Health Partners Integrated Cancer Centre, Department of Research Oncology, Guy's Hospital Campus, Great Maze Pond, London SE1 9RT, UK; Department of Immunology, Barnet Hospital, Royal Free London NHS Foundation Trust, Barnet, Hertfordshire, EN5 3DJ, UK; Department of Clinical Immunology and Allergy, King's College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK.
authors.forename: John
authors.initials: J
authors.lastname: Maher
mesh_terms: D019337:Hematologic Neoplasms / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011993:Recombinant Fusion Proteins
keywords: Cancer; Chimeric antigen receptor; Immunotherapy; Solid tumours; T-cells