Frontiers in Immunology (Sep 2013)
‘Model T’ cells: a time-tested vehicle for gene therapy
Abstract
T lymphocytes first carried foreign genes safely into humans over two decades ago. Since these pioneering studies, scientific techniques to better understand the genomic landscape of cells has directly led to a more sophisticated appreciation of the diversity, functional complexity, and therapeutic potential of T cells. Through the use of mouse models, we now know the function of the many genes that are critical for T cells to recognize foreign, mutated, or self-antigens and the factors responsible for the lineage diversification of T cells that lead to inhibitory or stimulatory immune responses. This knowledge combined with well-established modalities to introduce genes into T cells allows for the design of effector and memory CD8 and CD4 T lymphocytes specific for viral, fungal, bacterial, parasitic and tumor antigens and to design regulatory lymphocytes specific for the self-antigens responsible for autoimmune and inflammatory diseases. Here, I review strategies for designing the ideal T cell by introducing genes controlling 1) the secretion of cytokines/chemokines and their receptors, 2) T cell receptor specificity, 3) chimeric-antigen receptors that enable for the recognition of surface antigens in an MHC-independent fashion, 4) co-stimulatory/inhibitory surface molecules, and 5) disease defining single-gene factors.
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