mRNA vaccination with charge-altering releasable transporters elicits human T cell responses and cures established tumors in mice.

作者: Ole A. W. Haabeth , Timothy R. Blake , Colin J. McKinlay , Robert M. Waymouth , Paul A. Wender

DOI: 10.1073/PNAS.1810002115

关键词:

摘要: In vivo delivery of antigen-encoding mRNA is a promising approach to personalized cancer treatment. The therapeutic efficacy vaccines contingent on safe and efficient gene delivery, biological stability the mRNA, immunological properties vaccine. Here we describe development evaluation versatile highly vaccine-delivery system that employs charge-altering releasable transporters (CARTs) deliver antigen-coding antigen-presenting cells (APCs). We demonstrate in human peripheral blood mononuclear CART can activate robust antigen-specific immune response against mRNA-encoded viral epitopes. an established mouse model, CARTs preferentially target professional APCs secondary lymphoid organs upon i.v. injections local s.c. injection. Finally, show coformulated with Toll-like receptor ligand simultaneously transfect generate treat cure mice large, tumors.

参考文章(34)
Murali Ramamoorth, Aparna Narvekar, Non Viral Vectors in Gene Therapy- An Overview JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH. ,vol. 9, ,(2015) , 10.7860/JCDR/2015/10443.5394
Ugur Sahin, Katalin Karikó, Özlem Türeci, mRNA-based therapeutics — developing a new class of drugs Nature Reviews Drug Discovery. ,vol. 13, pp. 759- 780 ,(2014) , 10.1038/NRD4278
Aurélien Marabelle, Holbrook Kohrt, Idit Sagiv-Barfi, Bahareh Ajami, Robert C. Axtell, Gang Zhou, Ranjani Rajapaksa, Michael R. Green, James Torchia, Joshua Brody, Richard Luong, Michael D. Rosenblum, Lawrence Steinman, Hyam I. Levitsky, Victor Tse, Ronald Levy, Depleting tumor-specific Tregs at a single site eradicates disseminated tumors Journal of Clinical Investigation. ,vol. 123, pp. 2447- 2463 ,(2013) , 10.1172/JCI73340
W.-Z. Zhou, D.S.B. Hoon, S.K.S. Huang, S. Fujii, K. Hashimoto, R. Morishita, Y. Kaneda, RNA melanoma vaccine: induction of antitumor immunity by human glycoprotein 100 mRNA immunization. Human Gene Therapy. ,vol. 10, pp. 2719- 2724 ,(1999) , 10.1089/10430349950016762
T. Friedmann, R. Roblin, Gene Therapy for Human Genetic Disease? Science. ,vol. 175, pp. 949- 955 ,(1972) , 10.1126/SCIENCE.175.4025.949
Guoqing Zhang, Jianbin Chen, Sarah J. Payne, Steven E. Kooi, J. N. Demas, Cassandra L. Fraser, Multi-emissive difluoroboron dibenzoylmethane polylactide exhibiting intense fluorescence and oxygen-sensitive room-temperature phosphorescence. Journal of the American Chemical Society. ,vol. 129, pp. 8942- 8943 ,(2007) , 10.1021/JA0720255
Burkhard Ludewig, Federica Barchiesi, Marcus Pericin, Rolf M Zinkernagel, Hans Hengartner, Reto A Schwendener, In vivo antigen loading and activation of dendritic cells via a liposomal peptide vaccine mediates protective antiviral and anti-tumour immunity. Vaccine. ,vol. 19, pp. 23- 32 ,(2000) , 10.1016/S0264-410X(00)00163-8
Hongtao Lv, Shubiao Zhang, Bing Wang, Shaohui Cui, Jie Yan, Toxicity of cationic lipids and cationic polymers in gene delivery. Journal of Controlled Release. ,vol. 114, pp. 100- 109 ,(2006) , 10.1016/J.JCONREL.2006.04.014
Jordan J. Green, Robert Langer, Daniel G. Anderson, A Combinatorial Polymer Library Approach Yields Insight into Nonviral Gene Delivery Accounts of Chemical Research. ,vol. 41, pp. 749- 759 ,(2008) , 10.1021/AR7002336
Zhi-Chun Ding, Bruce R. Blazar, Andrew L. Mellor, David H. Munn, Gang Zhou, Chemotherapy rescues tumor-driven aberrant CD4+ T-cell differentiation and restores an activated polyfunctional helper phenotype Blood. ,vol. 115, pp. 2397- 2406 ,(2010) , 10.1182/BLOOD-2009-11-253336