In situ programming of leukaemia-specific T cellsusing synthetic DNA nanocarriers
Nature Nanotechnology 2017, Vol 12, p813
by Matthias Stephan in the Clinical Research Division of the Fred Hutchinson Cancer Research Center in Seattle, WA.
With funding from the Fred Hutchinson Cancer Research Center’s Immunotherapy Initiative with funds provided by the Bezos Family Foundation. Additional funds from the Leukemia and Lymphoma Society, the NSF, and the NIH.

Abstract: An emerging approach for treating cancer involves programming patient-derived T cells with genes encoding disease-specific chimeric antigen receptors (CARs), so that they can combat tumour cells once they are reinfused. Although trials of this therapy have produced impressive results, the in vitro methods they require to generate large numbers of tumour-specific T cells are too elaborate for widespread application to treat cancer patients. Here, we describe a method to quickly program circulating T cells with tumour-recognizing capabilities, thus avoiding these complications. Specifically, we demonstrate that DNA-carrying nanoparticles can efficiently introduce leukaemia-targeting CAR genes into T-cell nuclei, thereby bringing about long-term disease remission. These polymer nanoparticles are easy to manufacture in a stable form, which simplifies storage and reduces cost. Our technology may therefore provide a practical, broadly applicable treatment that can generate anti-tumour immunity ‘on demand’ for oncologists in a variety of settings.

Dinner party tag line: I just read a new article out of Seattle where scientists were able to turn on immune cells in your body to fight and eliminate leukemia in mice using there DNA modifying nanoparticles. This new formulation would avoid chemotherapeutic pre-treatment for people with leukemia while maintaining and/or exceeding current efficacy rates.

Future Business Potential: The results from this paper are truly amazing considering the response they are achieving through uptake of their nanoparticles by T-cells and the reduction in off-site deposition of their nanoparticles. Mechanistically, I think there is a lot of potential for this immunotherapeutic approach to treating specific leukemia patients. However, there are still many many hurdles they will need to overcome before ever even reaching first-in-human trials. Such as future detailed characterization of the particles, their stability in dry and wet form, the potential toxicity of broken, pieces of the nanoparticles, the effect of different sized particles. This list goes on and on from their. Then, they will need to move to larger animal models to prove efficacy and safety there as well. Finally, human clinical trials tend to offer a whole host of new problems. Therefore, while this is a great mechanistic finding, I think it will be a very long time before we see these particles or this approach used in humans.