| Title: |
RNAdjuvant®, a novel, highly-potent RNA-based adjuvant, combines strong immunostimulatory capacities with a favorable safety profile |
| Authors: |
Lutz, Johannes; Heidenreich, Regina; Mehr, Keyvan Tadjalli; Noth, Janine; Koch, Sven D; Döner, Fatma; Hong, Henoch S; Melber, Karl; Dähling, Angelika; Roos, Tilmann; Kowalczyk, Aleksandra; Baumhof, Patrick; Scheel, Birgit; Voss, Söhnke; Kallen, Karl-Josef; Fotin-Mleczek, Mariola; Gnad-Vogt, Ulrike |
| Source: |
The Journal of Immunology ; volume 198, issue Supplement_1, page 79.7-79.7 ; ISSN 0022-1767 1550-6606 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2017 |
| Description: |
Purified recombinant proteins and peptides, which are currently under development in various anti-cancer vaccination approaches, lack sufficient immunogenicity. Therefore, potent adjuvants are needed to induce strong and persistent anti-tumor immunity. However, currently only few adjuvants are licensed, most of which primarily enhance antibody, but not T cell responses. Here, we demonstrate that a novel, well defined, and thoroughly characterized RNA-based adjuvant mediates balanced and long-lasting humoral and cellular immune responses. Our adjuvant significantly enhances anti-tumor immunity, and even complete tumor rejection can be achieved as shown for the syngeneic TC-1 tumor model, a murine model of human HPV-induced cervical cancer. Our adjuvant acts locally, promoting strong but transient up-regulation of anti-viral and pro-inflammatory cytokines, CXCR3-ligands and cytoplasmic RNA sensors at the injection site, avoiding any systemic cytokine release. A phase I first in man clinical trial testing different doses of RNAdjuvant® alone and in combination with reduced doses of the licensed rabies vaccine Rabipur® was successfully conducted in 43 subjects. Healthy volunteers received 2 intramuscular injections of RNAdjuvant® on days 0 and 21, either alone or in combination with 1/20 or 1/10 of the licensed Rabipur® dose. Virus neutralizing antibody titers (VNTs) measured on days 14 and 28 revealed a significant increase in median VNTs in subjects with RNAdjuvant® compared to their respective control group with 1/10 dose Rabipur® alone. In summary, our data suggest that RNAdjuvant® represents a novel, highly efficacious adjuvant candidate that can enhance cellular and humoral immune responses. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.4049/jimmunol.198.supp.79.7 |
| Availability: |
https://doi.org/10.4049/jimmunol.198.supp.79.7; https://academic.oup.com/jimmunol/article/198/Supplement_1/79.7/7971522 |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.FD27CDD0 |
| Database: |
BASE |