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.

Immunotherapy with CTL restricted by nonself MHC.

In the past years a number of target antigens recognized by cytotoxic T-lymphocytes (CTL) have been identified in human malignancies. In most cases, the CTL-recognized antigens did not arise from mutations, but were instead encoded by genes that were identical in normal and tumor cells. Gene expression in normal tissues may result in tolerance of high avidity CTL, leaving behind low avidity CTL that cannot provide effective immunity against tumors expressing the relevant target antigens.