Primary T lymphocytes as targets for gene therapy

Peripheral blood T lymphocytes have been considered an attractive target fo r gene therapy applications. They can be easily harvested and readily expan ded ex vivo. The transduction efficiency of primary human lymphocytes with standard retroviral vectors approaches 50% or more using optimized methods of gene transfer. Other methods of gene transfer, including adenoviral, ade no-associated viral, and lentiviral vectors, or nonviral techniques, have a lso been used for gene transfer into primary lymphocytes. Despite encouragi ng results in vitro, human clinical trials using retroviral vectors to tran sduce primary lymphocytes have been hindered by low expression levels of tr ansgenes and immune responses against transgene products. Strategies to ove rcome these problems need to be developed.