T-Cell Gene Therapy in Cancer Immunotherapy: Why It Is No Longer Just CARs on The Road
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T-Cell Gene Therapy in Cancer Immunotherapy : Why It Is No Longer Just CARs on The Road. / Crowther, Michael D.; Svane, Inge Marie; Met, Özcan.
In: Cells, Vol. 9, No. 7, 1588, 2020.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - T-Cell Gene Therapy in Cancer Immunotherapy
T2 - Why It Is No Longer Just CARs on The Road
AU - Crowther, Michael D.
AU - Svane, Inge Marie
AU - Met, Özcan
PY - 2020
Y1 - 2020
N2 - T-cells have a natural ability to fight cancer cells in the tumour microenvironment. Due to thymic selection and tissue-driven immunomodulation, these cancer-fighting T-cells are generally low in number and exhausted. One way to overcome these issues is to genetically alter T-cells to improve their effectiveness. This process can involve introducing a receptor that has high affinity for a tumour antigen, with two promising candidates known as chimeric-antigen receptors (CARs), or T-cell receptors (TCRs) with high tumour specificity. This review focuses on the editing of immune cells to introduce such novel receptors to improve immune responses to cancer. These new receptors redirect T-cells innate killing abilities to the appropriate target on cancer cells. CARs are modified receptors that recognise whole proteins on the surface of cancer cells. They have been shown to be very effective in haematological malignancies but have limited documented efficacy in solid cancers. TCRs recognise internal antigens and therefore enable targeting of a much wider range of antigens. TCRs require major histocompatibility complex (MHC) restriction but novel TCRs may have broader antigen recognition. Moreover, there are multiple cell types which can be used as targets to improve the "off-the-shelf" capabilities of these genetic engineering methods.
AB - T-cells have a natural ability to fight cancer cells in the tumour microenvironment. Due to thymic selection and tissue-driven immunomodulation, these cancer-fighting T-cells are generally low in number and exhausted. One way to overcome these issues is to genetically alter T-cells to improve their effectiveness. This process can involve introducing a receptor that has high affinity for a tumour antigen, with two promising candidates known as chimeric-antigen receptors (CARs), or T-cell receptors (TCRs) with high tumour specificity. This review focuses on the editing of immune cells to introduce such novel receptors to improve immune responses to cancer. These new receptors redirect T-cells innate killing abilities to the appropriate target on cancer cells. CARs are modified receptors that recognise whole proteins on the surface of cancer cells. They have been shown to be very effective in haematological malignancies but have limited documented efficacy in solid cancers. TCRs recognise internal antigens and therefore enable targeting of a much wider range of antigens. TCRs require major histocompatibility complex (MHC) restriction but novel TCRs may have broader antigen recognition. Moreover, there are multiple cell types which can be used as targets to improve the "off-the-shelf" capabilities of these genetic engineering methods.
KW - cancer
KW - CAR-T
KW - immunotherapy
KW - T-cells
KW - TCR-T
U2 - 10.3390/cells9071588
DO - 10.3390/cells9071588
M3 - Review
C2 - 32630096
AN - SCOPUS:85087693260
VL - 9
JO - Cells
JF - Cells
SN - 2073-4409
IS - 7
M1 - 1588
ER -
ID: 244919216