AcTaferon · Revitalizing the clinical potential of type I IFNs in fighting influenza A virus infections with AcTaferon.
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-05-01 → 2018-12-31
- EU contribution
- €144,230
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Revitalizing the clinical potential of type I IFNs in fighting influenza A virus infections with AcTaferon.
The flu, caused by seasonal influenza epidemics and occasional pandemics, remains a serious health threat associated with substantial morbidity, mortality and economic loss due to sickness leave. Direct-acting antivirals (DAAs) that inhibit virus replication, and prophylactic vaccines are currently the most effective antiviral strategies. However, the emergence of numerous DAA- and vaccine-resistant virus strains presses the need to develop improved drugs against different influenza variants and subtypes. AcTaferons (Activity by Targeting interferons) are a novel class of engineered interferons that maximally take advantage of a sophisticated, natural defense system that evolutionary arose to combat viral infections. Cells infected with a virus naturally produce the alarm signal type I interferon (IFN), which upon binding to the IFN receptor on infected and neighbouring cells activates an antiviral response that interferes with the viral replication and spread throughout the body. IFN binding on immune cells further stimulates our immune system to fight the infection. Based on their antiviral and immunostimulatory effects, type I interferons were believed to be the miracle drug to tackle viruses. However, clinical IFN applications remained limited as IFN drugs cause severe side effects due to unwanted IFN binding to IFN receptors present all over the body, resulting in widespread, aspecific action of the drug. AcTaferon circumvents these side effects by selective targeting of IFN to specific cell types. AcTaferon remains inactive “en route” through the body and unveils its antiviral activity only on specific target cells. This project aims to generate virus-targeted AcTaferons (O1) and to evaluate the prophylactic and therapeutic potential of virus- and immune cell-targeted AcTaferons to restrict influenza infection in vitro (O2 and O3) and in vivo (O4).
Data: CORDIS, © European Union
Project objective
Based on their antiviral and antitumor effect, type I interferons (IFNs) were believed to be the miracle drug to tackle viruses and cancer. However, clinical IFN applications remained limited due to severe side effects resulting from widespread cellular sensitivity to IFN, which limits the administrable doses. Hence, the drug concentration at the desired infection or tumor site is often too low to be fully therapeutic efficient. AcTaferon (Activated-by-Targeting interferon), co-developed by Prof. Uzé, circumvents these obstacles. By fusing an IFN mutant with strongly reduced receptor binding affinity to a targeting moiety that recognizes a surface marker on specific cells, AcTaferon remains inactive “en route” through the body and unveils its biological activity only on specific target cells. Robust tumor regression without side effects and preliminary antiviral effects underscore the huge clinical potential of AcTaferon to fight cancer and viral diseases. By combining the AcTaferon and influenza expertise of Prof. Uzé and Prof. Saelens, respectively, this interdisciplinary project offers the opportunity to broaden the innovative AcTaferon therapeutic strategy from the cancer to the viral infection field. Influenza A was selected as a pilot target as seasonal influenza A epidemics and occasional pandemics remain a serious health threat causing substantial morbidity and mortality. Influenza A-targeted AcTaferons will be developed and analyzed in relevant in vitro and in vivo models. Eventually, all knowledge will be transferred to Orionis, a company that will implement the AcTaferon technology to develop novel drugs. My background on the intracellular processes that negatively regulate cytokine receptors and hence influence the cellular sensitivity to a (therapeutic) cytokine is an asset to this project. I will be able to extend my fundamental research experience with applied cytokine research, which may extend into a new academic or industrial research pipeline.
Original text from CORDIS.
Participants
- CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union