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) an HIV tat transport domain;
(b) at least two proteotlytic cleavage sites cleaved by the furin family of enzymes;
(c) a first peptide epitope recognized by an antigen specific receptor on an effector CD4 + T lymphocyte wherein the first peptide epitope is between 9 and 30 amino acids in length; and
(d) at least one additional peptide epitope recognized by an antigen specific receptor on an effector CD8 + T lymphocyte wherein the at least one additional epitope is between 8 and 12 amino acids in length;
wherein there is a cleavage site between each of the peptide epitopes and between the peptide epitopes and the HIV tat transport domain in the fusion agent.
2. The fusion agent of claim 1 wherein the first peptide epitope can bind to a major histocompatability (MHC) class II molecule.
3. The fusion agent of claim 1 wherein the at least one additional peptide epitode can bind to a major histocompatability complex (MHC) class I molecule.
4. The fusion agent of claim 1 wherein the HIV tat transport domain is the HIV tat transport domain of SEQ ID NO: 1.
5. The fusion agent of claim 1 comprising at least two additional peptide epitodes recognized by an antigen specific receptor on an CD8 + T lymphocyte.
6. The fusion agent of claim 1 , wherein the peptide epitode recognized by an antigen specific receptor on an CD4 + T lymphocyte is a MAGE epitope.
7. The fusion agent of claim 6 , comprising two additional epitopes recognized by antigen specific receptors on effector CD8 + T lymphocytes, wherein the two additional epitopes are MAGE epitopes.