Work

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

Year: 2018

Type: article

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

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1810002115

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

Institutions: Oslo University Hospital, Stanford Medicine, Stanford Cancer Institute, Stanford University

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green