With the exception of viral-induced malignances such as cervical cancer, high-affinity proinflammatory T cells
specific for tumor-associated antigens (TAA) are either deleted or rendered anergic as a consequence of central and
peripheral tolerance. Reprogramming of peripheral blood-derived T cells while preserving their full functional potential to
recognize and kill tumor cells is thus required to circumvent negative selection processes. One tactic for redirecting
specificity is through genetic modification of T cells to express a chimeric antigen receptor (CAR) targeting a TAA such
as CD19, which is expressed on B-lineage malignancies, and their subsequent adoptive transfer into cancer patients.
Transposon-based gene transfer is an alternative method to retroviral transduction for integrating such transgenes into the
T-cell genome. The Sleeping Beauty (SB) transposon system is a safe and low-cost technique for engineering T cells to
express a CD19-specific CAR from a plasmid. This gene-transfer approach provides sufficient transgene integration for
retrieval of clinically sufficient numbers of CAR+ T cells for clinical translation into the first-in-human clinical trial
already enrolling patients.
Keywords: Cancer, DNA transposons, gene therapy, T cells, transposition, Sleeping Beauty
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