A method for producing from stem cells a large quantity of human immune cells capable of killing tumor cells in mice is presented in a paper published online this week in Nature Biotechnology. The approach may make it easier to implement cancer ‘immunotherapies’ – a suite of treatments that activate the immune system to attack tumors.
Most cancer immunotherapy strategies require isolation of immune cells called T cells from the blood of cancer patients. However, T cells that specifically recognize and kill only tumor cells but not healthy cells are very rare, and the problem is how to generate large numbers of such cells. Previous work has shown that either T cells can be engineered to express tumor-specific receptors or they can be grown in large numbers using ‘reprogramming’ technology.
Now, Michel Sadelain and colleagues combined these methods to grow an unlimited supply of tumor-specific T cells and demonstrated the ability of the cells to control tumors in mice. The authors started with a small number of T cells isolated from the blood of a healthy person, reprogrammed the cells into stem cells, and engineered the stem cells to express a tumor-specific receptor. The stem cells were coaxed to reacquire their original T cell properties, expanded to large numbers, and then injected into tumor-bearing mice. Sadelain and colleagues found that the lab-grown T cells suppressed tumor growth in the mice to an extent similar to that of natural T cells that were isolated from the blood of the same person and engineered to express the same tumor-specific receptor. If the approach can be translated to the clinic, many more patients could become eligible to receive this type of cancer immunotherapy.
Maria Themeli, Christopher C Kloss, Giovanni Ciriello, Victor D Fedorov, Fabiana Perna, Mithat Gonen & Michel Sadelain
Nature Biotechnology (2013) doi:10.1038/nbt.2678