Journal
EXPERT OPINION ON BIOLOGICAL THERAPY
Volume 5, Issue 9, Pages 1183-1192Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/14712598.5.9.1183
Keywords
adoptive transfer; allo-restricted CTL; immunotherapy; MDM2; T cell tolerance; TCR gene transfer; tumour-associated antigen
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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 Tcell 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.
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