Broadly expressed tumour-associated proteins as targets for cytotoxic T lymphocyte-based cancer immunotherapy.
T cell-based antigen-specific immunotherapy targeting self-proteins aberrantly expressed in many tumours offers the potential for widely applicable cancer immunotherapy, but carries the risk of autoimmunity. Immunological tolerance represents an inherent limitation of cancer vaccines targeting such broadly expressed tumour-associated proteins. Therefore, strategies to circumvent T cell tolerance have been developed and, when combined with T cell receptor (TCR) gene transfer technology, can generate highly avid tumour-reactive patient cytotoxic T lymphocytes (CTLs) specific for peptide epitopes of tumour-associated proteins. This review analyses the level of tolerance to broadly expressed tumour-associated proteins in the autologous T cell repertoire, assesses strategies that have been developed to circumvent T cell tolerance to such antigens, and evaluates the prospects for effective immunotherapy targeting broadly expressed tumour-associated proteins.
Bendle
Gavin M
GM
Royal Free Hospital, Department of Immunology and Molecular Pathology, University College London, London, NW3 2QG, UK.
Holler
Angelika
A
Downs
Anne-Marie
AM
Xue
Shao-An
SA
Stauss
Hans J
HJ
D019264:Adoptive Transfer; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015316:Genetic Therapy; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods; D023421:Models, Animal; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000637:transplantation
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D011948:Receptors, Antigen, T-Cell; D051736:Proto-Oncogene Proteins c-mdm2