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Blood Rev. 2006 Mar;20(2):61-9. Epub 2005 Jun 22.

Generation of tumor-specific T-cell therapies.

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Department of Immunology, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.


Antigen-specific tumor immunotherapy remains an attractive strategy for the treatment of malignancies. In this review we will discuss why, despite the identification of large numbers of T cell recognised tumor antigens, effective immunotherapy remains a formidable challenge. Effective strategies are needed to deal with the tolerogenic properties of many tumor antigens, and with the immunocompromised status of patients. We discuss different methods of generating tumor-specific T cells which are currently being evaluated in clinical practice, such as vaccination and adoptive transfer of tumor antigen-specific T cells. Finally, we shall discuss novel strategies in development, such as the adoptive transfer of T cell receptor (TCR) gene modified T cells to establish antigen-specific immunity in patients with leukemia and solid cancers. The transfer of validated high avidity TCRs, isolated from 'non-tolerant' repertoires or produced by in vitro affinity maturation, can serve to equip patient T cells with new anti-tumor specificities that are not naturally present in the autologous repertoire. TCR transfer into CD4(+) and CD8(+) T cells can serve to harness the function of both helper and cytotoxic T cells for tumor elimination and establishment of long-term tumor immunity.

[Indexed for MEDLINE]

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