ACS Nano. 11, 10724–10732 (2017)

Adoptive T-cell transfer is a cancer immunotherapy strategy that involves extraction of T cells from a patient, ex vivo expansion and activation, and reinfusion in the body for tumour targeting. During the ex vivo treatment, T cells are trained to recognize cancer biomarkers on exposure to antigen-presenting cells (APC), which reprogrammes them into antigen-specific cytotoxic T cells (CTLs) for tumour recognition and killing. The use of natural APCs, however, hampers precise control over T-cell stimulation and often leads to low reproducibility and poor survival of the CTLs.

Now, Zhang et al. engineer an artificial APC that consists of an iron oxide magnetic nanocluster coated with a leukocyte membrane containing azide-modified lipids, which provide useful click-chemistry handles for functionalization with specific T-cell stimulation moieties. The leukocyte membrane also confers biocompatibility and endows the particles with a fluid coat that allows better interaction with the T cells. In comparison with activation using soluble antibodies, the authors show that their artificial APCs lead to more efficient T-cell expansion and to increased cytotoxicity. Leveraging on the magnetic properties of the APC–CTL complex, which is stable enough to survive intravenous injection in animals, the authors also show that they can direct the APC–CTL specifically to tumours and image its distribution within tissues using MRI. Delivery of the magnetically guided APC–CTL complex results in reduced tumour growth, minor side effects and increased animal survival when compared to controls receiving only CTLs or the APC–CTL complex with no magnetic guidance.