Immunology in the clinic review series; focus on cancer: double trouble for tumours: bi‐functional and redirected T cells as effective cancer immunotherapies

• Published in: Clinical and experimental immunology 2012-02, Vol.167 (2), p.216-225
• Main Authors: Marr, L. A., Gilham, D. E., Campbell, J. D. M., Fraser, A. R.
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Antigens, Neoplasm - immunology; Biological and medical sciences; bi‐functional; Cancer; CAR; Clinical trials; Clinical Trials as Topic; Diabetes mellitus; Diets; Fundamental and applied biological sciences. Psychology; Genetic Vectors; Humans; Hypersensitivity; Immune system; Immunologic Surveillance; Immunosurveillance; Immunotherapy; Immunotherapy - methods; Immunotherapy, Adoptive; Life span; Lymphocytes; Lymphocytes T; Metabolic disorders; Mice; Molecular Targeted Therapy; Neoplasms - immunology; Neoplasms - therapy; Radiotherapy; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; redirected; Review; Reviews; Surgery; T cell receptors; T cell therapy; T-Cell Antigen Receptor Specificity; T-cell receptor; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - transplantation; Transduction, Genetic; Transplantation Conditioning - methods; Tumor Escape; Tumor Microenvironment - immunology; Tumors
• ISSN: 0009-9104; 1365-2249; 1365-2249
• DOI: 10.1111/j.1365-2249.2011.04517.x

Summary OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES Metabolic Diseases, Host Responses, Allergies, Autoinflammatory Diseases, Type 1 diabetes and viruses. 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.