Feb. 13, 2008 A subset of immune cells known as iNKT cells have been shown to have antitumor activity. However, if mice are injected with a soluble form of a molecule that activates them (alpha-GalCer), the cells are only activated for a short time and then become dormant.
Now, Alena Donda and colleagues at the University of Lausanne, Switzerland, have identified a way to activate mouse iNKT cells for longer periods of time and to target them to tumors.
In the study, mice were given a series of injections of alpha-GalCer bound to a soluble form of a protein known as CD1d (alpha-GalCer/sCD1d). This led to sustained iNKT cell activation as well as activation of other immune cell types important for antitumor immunity -- NK cells and DCs.
Furthermore, when a form of the alpha-GalCer/sCD1d fused to a molecule (known as a scFv antibody fragment) that targeted the protein HER2 was administered to mice injected with tumor cells expressing HER2 two days earlier, the growth and metastasis of the tumor cells was inhibited.
This antitumor activity was associated with the accumulation of iNKT cells, NK cells, and DCs at the site of the tumor. The authors therefore suggested that targeting iNKT cells to tumors could provide a new approach to treating many forms of cancer.
Journal reference: Sustained activation and tumor targeting of NKT cells using a CD1d--anti-HER2--scFv fusion protein induces antitumor effects in mice. Journal of Clinical Investigation. February 7, 2008.
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