Chimeric antigen-specific t cell-activating polypeptides
View Patent ↗The invention provides an immunogenic or antigenic polypeptide containing a translocation domain, a peptide epitope, at least one biologically active agent, and cleavage sites. These polypeptides are useful for activating T cell responses.
1. A fusion agent comprising:
(a) a transport domain;
(b) at least two cleavage sites;
(c) a first peptide epitope recognized by an antigen specific receptor on an effector T lymphocyte or on an effector T lymphocyte precursor cell; and
(d) at least one additional peptide epitope recognized by an antigen specific receptor on an effector T lymphocyte or on an effector T lymphocyte precursor cell,
wherein each of the peptide epitopes in the fusion agent is 7-40 amino acids in length and there is a cleavage site between each of the peptide epitopes in the fusion agent.
2. The fusion agent of claim 1 , wherein the effector T lymphocyte is a cytotoxic T lymphocyte (CTL) and the effector T lymphocyte precursor cell is a CTL precursor cell.
3. The fusion agent of claim 1 , wherein the peptide epitope can bind to a major histocompatibility complex (MHC) class I molecule.
4. The fusion agent of claim 1 , wherein there is a cleavage site between the transport domain and the first peptide epitope.
5. The fusion agent of claim 1 , wherein the transport domain comprises all or part of a cleavage site.
6. The fusion agent of claim 1 , wherein the transport domain is a HIVtat domain (SEQ ID NO:1).
7. The fusion agent of claim 1 , wherein the at least two cleavage sites are proteolytic enzyme cleavage sites.
8. The fusion agent of claim 7 , wherein the proteolytic enzyme is a member of the furin family of enzymes.
9. The fusion agent of claim 1 , wherein the at least one additional peptide epitope is recognized by a CTL or a CTL precursor cell.
10. The fusion agent of claim 1 , wherein each of the peptide epitopes is 8-20 amino acids in length.
11. The fusion agent of claim 1 , wherein each of the peptide epitopes is 8-15 amino acids in length.
12. A fusion agent comprising:
(a) a transport domain;
(b) at least two cleavage sites;
(c) a first peptide epitope recognized by an antigen specific receptor on an effector T lymphocyte or on an effector T lymphocyte precursor cell; and
(d) at least one additional peptide epitope recognized by an antigen specific receptor on an effector T lymphocyte or on an effector T lymphocyte precursor cell,
wherein the transport domain is at the N terminus or at the C terminus of the fusion agent and there is a cleavage site between each of the peptide epitopes in the fusion agent.
13. The fusion agent of claim 12 , wherein the effector T lymphocyte is a cytotoxic T lymphocyte (CTL) and the effector T lymphocyte precursor cell is a CTL precursor cell.
14. The fusion agent of claim 12 , wherein the peptide epitope can bind to a major histocompatibility complex (MHC) class I molecule.
15. The fusion agent of claim 12 , wherein there is a cleavage site between the transport domain and the first peptide epitope.
16. The fusion agent of claim 12 , wherein the transport domain comprises all or part of a cleavage site.
17. The fusion agent of claim 12 , wherein the transport domain is a HIVtat domain (SEQ ID NO:1).
18. The fusion agent of claim 12 , wherein the at least two cleavage sites are proteolytic enzyme cleavage sites.
19. The fusion agent of claim 18 , wherein the proteolytic enzyme is a member of the furin family of enzymes.
20. The fusion agent of claim 12 , wherein the at least one additional peptide epitope is a second peptide epitope and is recognized by a CTL or a CTL precursor cell.