title: Immunology in the clinic review series; focus on cancer: double trouble for tumours: bi-functional and redirected T cells as effective cancer immunotherapies.
abstract: Cancer is one of the most important pathological conditions facing mankind in the 21st century, and is likely to become the most important cause of death as improvements continue in health, diet and life expectancy. The immune response is responsible for controlling nascent cancer through immunosurveillance. If tumours escape this control, they can develop into clinical cancer. Although surgery and chemo- or radiotherapy have improved survival rates significantly, there is a drive to reharness immune responses to treat disease. As T cells are one of the key immune cells in controlling cancer, research is under way to enhance their function and improve tumour targeting. This can be achieved by transduction with tumour-specific T cell receptor (TCR) or chimaeric antigen receptors (CAR) to generate redirected T cells. Virus-specific cells can also be transduced with TCR or CAR to create bi-functional T cells with specificity for both virus and tumour. In this review we outline the development and optimization of redirected and bi-functional T cells, and outline the results from current clinical trials using these cells. From this we discuss the challenges involved in generating effective anti-tumour responses while avoiding concomitant damage to normal tissues and organs.
authors.affiliation: Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: L A
authors.initials: LA
authors.lastname: Marr
authors.forename: D E
authors.initials: DE
authors.lastname: Gilham
authors.forename: J D M
authors.initials: JD
authors.lastname: Campbell
authors.forename: A R
authors.initials: AR
authors.lastname: Fraser
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D002986:Clinical Trials as Topic; D005822:Genetic Vectors; D006801:Humans; D007157:Immunologic Surveillance; D007167:Immunotherapy / Q000379:methods*; D016219:Immunotherapy, Adoptive; D051379:Mice; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D014161:Transduction, Genetic; D019172:Transplantation Conditioning / Q000379:methods; D019139:Tumor Escape; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins