Some genetic modification strategies for T cells.
| Aim . | Method . |
|---|---|
| GM-CSF indicates granulocyte-macrophage colony-stimulating factor; EBV, Eptsein-Barr virus; CTL, cytotoxic T lymphocyte; TGF, tumor growth factor; IL, interleukin. | |
| Modification of T-cell antigen specificity | Transduction of T cells with genes encoding TCR αβ chains obtained from antigen-specific T-cell clones |
| Modification of T-cell antigen specificity and function | Transduction of T cells with genes encoding chimeric antigen receptors containing costimulatory signaling molecules (CD28, 4-1BB, ICOS, OX40) |
| Enhancement of T-cell proliferative capacity and survival | Transduction of T cells with growth factor or cytokine genes (chimeric GM-CSF-IL2, IL-2, IL-15), antiapoptotic genes (BCL-2, BCL-XL), hTERT or siRNAs for proapoptotic molecules (CD95) Engineering dual-specific T cells that are specific for TAA and a potent immunogen (EBV-CTL expressing GD2CAR) |
| Increasing homing capacity of T cells to tumors | Transduction of T cells with chemokine receptor genes |
| Increasing T-cell resistance to tumor associated inhibitory molecules | Expression of dominant negative TGF-βII receptor or IL-12 gene by T cells Knockdown of GCN2 kinase pathway in T cells to protect them from IDO-mediated inhibition |
| Aim . | Method . |
|---|---|
| GM-CSF indicates granulocyte-macrophage colony-stimulating factor; EBV, Eptsein-Barr virus; CTL, cytotoxic T lymphocyte; TGF, tumor growth factor; IL, interleukin. | |
| Modification of T-cell antigen specificity | Transduction of T cells with genes encoding TCR αβ chains obtained from antigen-specific T-cell clones |
| Modification of T-cell antigen specificity and function | Transduction of T cells with genes encoding chimeric antigen receptors containing costimulatory signaling molecules (CD28, 4-1BB, ICOS, OX40) |
| Enhancement of T-cell proliferative capacity and survival | Transduction of T cells with growth factor or cytokine genes (chimeric GM-CSF-IL2, IL-2, IL-15), antiapoptotic genes (BCL-2, BCL-XL), hTERT or siRNAs for proapoptotic molecules (CD95) Engineering dual-specific T cells that are specific for TAA and a potent immunogen (EBV-CTL expressing GD2CAR) |
| Increasing homing capacity of T cells to tumors | Transduction of T cells with chemokine receptor genes |
| Increasing T-cell resistance to tumor associated inhibitory molecules | Expression of dominant negative TGF-βII receptor or IL-12 gene by T cells Knockdown of GCN2 kinase pathway in T cells to protect them from IDO-mediated inhibition |