Improving TCR Gene Therapy for Treatment of Haematological Malignancies

Figure 1

Populations of antigen specific T cells that can be generated by TCR gene transfer for use in adoptive immunotherapy. Retroviral gene transfer can be used to generate different populations of T cells for use in adoptive immunotherapy in the setting of haematological malignancy. Both CD8 and CD4 T cells can be transduced with class I-restricted TCR of the same specificity, targeting the same tumour antigen. Alternatively CD4 T cells can be transduced with class II-restricted TCR-specific tumour antigen presented by class II MHC. Antigen specific T regulatory cells can be generated by TCR transduction of CD4+ CD25+ T regulatory cells or CD4+ T cells can be cotransduced with TCR and FOXP3 resulting in production of antigen-specific converted CD4+ T regulatory cells. Antigen-specific T regulatory cells could be adoptively transferred in the context of HSCT or DLI to reduce harmful GvHD responses of T effector cells.