Generation of tumor-specific T-cell therapies.
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.
Department of Immunology, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
Emma
E
Morris
Dan
D
Hart
Liquan
L
Gao
Aristotle
A
Tsallios
Shao-An
SA
Xue
Hans
H
Stauss
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016867:Immunocompromised Host / Q000276:immunology; D017710:Lymphocyte Transfusion / Q000379:methods; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D011948:Receptors, Antigen, T-Cell