| Autor: |
Liu Y; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115., Adu-Berchie K; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115., Brockman JM; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115., Pezone M; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138., Zhang DKY; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115., Zhou J; Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana and Champaign, IL 61801., Pyrdol JW; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115., Wang H; Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana and Champaign, IL 61801., Wucherpfennig KW; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115., Mooney DJ; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115. |
| Abstrakt: |
Adoptive T cell transfer (ACT) therapies suffer from a number of limitations (e.g., poor control of solid tumors), and while combining ACT with cytokine therapy can enhance effectiveness, this also results in significant side effects. Here, we describe a nanotechnology approach to improve the efficacy of ACT therapies by metabolically labeling T cells with unnatural sugar nanoparticles, allowing direct conjugation of antitumor cytokines onto the T cell surface during the manufacturing process. This allows local, concentrated activity of otherwise toxic cytokines. This approach increases T cell infiltration into solid tumors, activates the host immune system toward a Type 1 response, encourages antigen spreading, and improves control of aggressive solid tumors and achieves complete blood cancer regression with otherwise noncurative doses of CAR-T cells. Overall, this method provides an effective and easily integrated approach to the current ACT manufacturing process to increase efficacy in various settings. |
