Prospects for immunotherapy of malignant disease.
The majority of T cell-recognized tumour antigens in humans are encoded by genes that are also present in normal tissues. Low levels of gene expression in normal cells can lead to the inactivation of high-avidity T cells by immunological tolerance mechanisms. As a consequence, low-avidity T cell responses in patients are often inadequate in providing tumour protection. Recently, several technologies have been developed to overcome tolerance, allowing the isolation of high-affinity, HLA-restricted receptors specific for tumour-associated peptide epitopes. Furthermore, transfer of HLA-restricted antigen receptors provides an opportunity to empower patient T cells with new tumour-reactive specificities that cannot be retrieved from the autologous T cell repertoire.
Morris
E C
EC
Department of Immunology, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London, UK.
Bendle
G M
GM
Stauss
H J
HJ
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000008:administration & dosage / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage; D005544:Forecasting; D015316:Genetic Therapy / Q000379:methods; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods / Q000639:trends*; D051379:Mice; D023421:Models, Animal; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic; D019139:Tumor Escape; D014611:Vaccination
D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell