Dec 18, 2020
Influenza-specific T-cell receptor (TCR)
Life Sciences, Immunology
- Influenza specific TCR
- Highly conserved epitope
- Several possible applications including new therapeutics, cellular therapy and vaccination
Influenza viruses cause severe and life threatening diseases in humans. Besides the known human influenza viruses, several other influenza virus species from animals such as swine or avian influenza exist, that are capable to be transferred to humans. Since influenza viruses are highly mutable, there is an ongoing threat of severe epidemics by mutated influenza viruses.
The invention is based on the identification and isolation of the TCR genes of influenza-specific cytotoxic T-lymphocytes (CTL) that can be used for therapy and prevention of influenza infections. The TCR recognizes a viral epitope (GILGFVFTL) in the influenza matrix, which is highly conserved in all influenza virus variants including human, swine and avian influenza. The epitope is presented by the HLA-A2, the most frequent HLA serotype worldwide (about 40% in Central Europe). The TCRs could be used for treatment of infected patients and for the preventive genetic immunization of healthy persons in the case of an emerging epidemic with a new virulent influenza strain.
Peripheral Blood mononuclear cells were electroporated with mRNA encoding a Influenza matrix protein (IMP) specific T-cell receptor. HLA-A2-positive T2-cells were incubated for one hour with the IMP-Peptide GILGFVFTL (IMP, FLU-M1:58-66) or with the HIV-RT-peptide ILKEPVHGV (IV9). Thereafter, 50 000 T2-cells were added to 150 00 PBMC and incubated over night in a g-IFN-ELISPOT-assay. Given are the numbers of g-IFN-secreting T-cells representing the peptide specific CTL. MOCK: PBMC, electroporated without TCR genes.
- as soluble TCR, fused to e.g. Fc receptor/Fc domain/cytokines/toxins/antibodies
- in cellular therapy, both autologous and allogenic; interesting for patients with life threatening drug resistant influenza infection, or new influenza variants when no vaccine is available yet
- in vaccine research, e.g. TCR transfected cells as standardized tool to check immunogenicity of attenuated vaccines (esp. in case of escape mutants)
- for genetic vaccination, esp. against highly pathogenic viruses such as avian flu without effective vaccine
Seeking for partners for further development and licensing.