| Autor: |
Parayath NN; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA., Stephan SB; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA., Koehne AL; Translational Pathology, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA., Nelson PS; Division of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.; Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, 98195, USA., Stephan MT; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. mstephan@fredhutch.org.; Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, 98195, USA. mstephan@fredhutch.org.; Department of Bioengineering and Molecular Engineering & Sciences Institute, University of Washington, Seattle, WA, 98195, USA. mstephan@fredhutch.org. |
| Abstrakt: |
Engineering chimeric antigen receptors (CAR) or T cell receptors (TCR) helps create disease-specific T cells for targeted therapy, but the cost and rigor associated with manufacturing engineered T cells ex vivo can be prohibitive, so programing T cells in vivo may be a viable alternative. Here we report an injectable nanocarrier that delivers in vitro-transcribed (IVT) CAR or TCR mRNA for transiently reprograming of circulating T cells to recognize disease-relevant antigens. In mouse models of human leukemia, prostate cancer and hepatitis B-induced hepatocellular carcinoma, repeated infusions of these polymer nanocarriers induce sufficient host T cells expressing tumor-specific CARs or virus-specific TCRs to cause disease regression at levels similar to bolus infusions of ex vivo engineered lymphocytes. Given their ease of manufacturing, distribution and administration, these nanocarriers, and the associated platforms, could become a therapeutic for a wide range of diseases. |
