Use of the allogeneic TCR repertoire to enhance anti-tumor immunity.
It is well established that antigen-specific T lymphocytes can inhibit tumor growth in humans and in mice, leading to complete tumor elimination in some cases. However, in many cases T cell immunity is unable to successfully control tumor progression. Since tumors are derived from normal tissues, most antigens are shared with normal tissues, although expression levels are usually elevated in malignant cells. Nevertheless, low-level expression in normal cells can be sufficient to render autologous T cells tolerant and thus unable to mount effective immune responses against tumors. Here, we review how allogeneic T cells can be used to isolate T cells that effectively recognise and kill tumor cells, but not normal cells with low level of antigen expression. The TCR of allogeneic T cells can be introduced into patient T cells to equip them with anti-tumor specificity that may not be present in the autologous T cell repertoire.
Department of Immunology, Tumour Immunology Section, Imperial College London, Hammersmith Hospital, London, UK.
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Xue
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Gillmore
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Gao
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Bendle
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A
Holler
A M
AM
Downs
A
A
Tsallios
F
F
Ramirez
Y
Y
Ghani
D
D
Hart
S
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Alcock
A
A
Tranter
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Morris
H J
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Stauss
D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy; D020544:Graft vs Leukemia Effect / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007938:Leukemia / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation; D014184:Transplantation, Homologous / Q000276:immunology; D025721:WT1 Proteins / Q000276:immunology
D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell; D025721:WT1 Proteins