mRNA Cancer Vaccines

Recent Results Cancer Res. 2016:209:61-85. doi: 10.1007/978-3-319-42934-2_5.

Abstract

mRNA cancer vaccines are a relatively new class of vaccines, which combine the potential of mRNA to encode for almost any protein with an excellent safety profile and a flexible production process. The most straightforward use of mRNA vaccines in oncologic settings is the immunization of patients with mRNA vaccines encoding tumor-associated antigens (TAAs). This is exemplified by the RNActive® technology, which induces balanced humoral and cellular immune responses in animal models and is currently evaluated in several clinical trials for oncologic indications. A second application of mRNA vaccines is the production of personalized vaccines. This is possible because mRNA vaccines are produced by a generic process, which can be used to quickly produce mRNA vaccines targeting patient-specific neoantigens that are identified by analyzing the tumor exome. Apart from being used directly to vaccinate patients, mRNAs can also be used in cellular therapies to transfect patient-derived cells in vitro and infuse the manipulated cells back into the patient. One such application is the transfection of patient-derived dendritic cells (DCs) with mRNAs encoding TAAs, which leads to the presentation of TAA-derived peptides on the DCs and an activation of antigen-specific T cells in vivo. A second application is the transfection of patient-derived T cells with mRNAs encoding chimeric antigen receptors, which allows the T cells to directly recognize a specific antigen expressed on the tumor. In this chapter, we will review preclinical and clinical data for the different approaches.

Keywords: Chimeric antigen receptor (CAR) T cell immunotherapy; Personalized mRNA vaccines; RNActive® vaccines; mRNA-pulsed dendritic cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Cancer Vaccines / genetics*
  • Cancer Vaccines / immunology
  • Cancer Vaccines / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / transplantation
  • Gene Expression Regulation, Neoplastic
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • RNA, Messenger / genetics*
  • RNA, Messenger / immunology
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell / biosynthesis
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / transplantation

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • RNA, Messenger
  • Receptors, Antigen, T-Cell