In:
The Journal of Immunology, The American Association of Immunologists, Vol. 198, No. 1_Supplement ( 2017-05-01), p. 79.7-79.7
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.198.Supp.79.7
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2017
detail.hit.zdb_id:
1475085-5
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