Special Section on Cancer Gene Therapy
Highly potent mRNA based cancer vaccines represent an attractive platform for combination therapies supporting an improved therapeutic effect
Article first published online: 27 JUN 2012
Copyright © 2012 John Wiley & Sons, Ltd.
The Journal of Gene Medicine
Volume 14, Issue 6, pages 428–439, June 2012
How to Cite
Fotin-Mleczek, M., Zanzinger, K., Heidenreich, R., Lorenz, C., Thess, A., Duchardt, K. M. and Kallen, K.-J. (2012), Highly potent mRNA based cancer vaccines represent an attractive platform for combination therapies supporting an improved therapeutic effect. J. Gene Med., 14: 428–439. doi: 10.1002/jgm.2605
- Issue published online: 27 JUN 2012
- Article first published online: 27 JUN 2012
- Accepted manuscript online: 19 JAN 2012 09:41PM EST
- Manuscript Accepted: 5 JAN 2012
- Manuscript Received: 16 SEP 2011
- cancer vaccine;
- ribonucleic acid;
Direct vaccination with mRNA encoding tumor antigens is a novel and promising approach in cancer immunotherapy. CureVac's mRNA vaccines contain free and protamine-complexed mRNA. Such two-component mRNA vaccines support both antigen expression and immune stimulation. These self-adjuvanting RNA vaccines, administered intradermally without any additional adjuvant, induce a comprehensive balanced immune response, comprising antigen specific CD4+ T cells, CD8+ T cells and B cells. The balanced immune response results in a strong anti-tumor effect and complete protection against antigen positive tumor cells. This tumor inhibition elicited by mRNA vaccines is a result of the concerted action of different players. After just two intradermal vaccinations, we observe multiple changes at the tumor site, including the up-regulation of many genes connected to T and natural killer cell activation, as well as genes responsible for improved infiltration of immune cells into the tumor via chemotaxis. The two-component mRNA vaccines induce a very fast and boostable immune response. Therefore, the vaccination schedules can be adjusted to suit the clinical situation. Moreover, by combining the mRNA vaccines with therapies in clinical use (chemotherapy or anti-CTLA-4 antibody therapy), an even more effective anti-tumor response can be elicited. The first clinical data obtained from two separate Phase I/IIa trials conducted in PCA (prostate cancer) and NSCLC (non-small cell lung carcinoma) patients have shown that the two-component mRNA vaccines are safe, well tolerated and highly immunogenic in humans. Copyright © 2012 John Wiley & Sons, Ltd.