Chimeric T-cell receptors for the targeting of cancer cells

Genetic engineering of human T lymphocytes to express tumor antigen-specific chimeric immune receptors is an attractive means for providing large numbers of effector cells for adoptive immunotherapy. Major mechanisms of tumor escape from immune recognition are efficiently bypassed. Although adoptive transfer of chimeric receptor-expressing peripheral blood-derived T lymphocytes has produced some anti-tumor activity in mice, the first clinical studies have revealed a disappointing lack of correlation between in vitro cytotoxicity and therapeutic efficacy. The most pertinent issue is that chimeric T cells fail to expand and rapidly lose their function in vivo. Potential strategies to enhance the therapeutic value of chimeric receptor-modified cells by preventing their functional inactivation in vivo are currently being investigated.