Polypeptides capable of binding to CD64 comprising one or more heterologous T cell epitopes and their uses
View Patent ↗The invention relates to the use of a polypeptide that comprises i) a first portion comprising the part of human Fc that binds to CD64, and ii) a second portion comprising one or more heterologous T cell epitopes for stimulating a cytotoxic T cell response. The polypeptide may be an antibody that may be used to stimulate a cytotoxic T cell response against pathogens and tumor cells in patients in need of such treatment.
1. A method for stimulating a CD8 cytotoxic T cell response in a human patient, comprising administering to the patient a therapeutically effective amount of an antibody protein that includes (i) human FcγI, and (ii) a single heterologous CD8 cytotoxic T cell epitope,
wherein the single heterologous CD8 cytotoxic T cell epitope has been substituted into a complementarity determining region (CDR) of the antibody protein that has similar size and charge as the epitope, and the first amino acid downstream of the epitope has been chosen from the group consisting of G, K, R, and S so that the epitope is cleaved, at its C-terminus, in the proteasome, to thereby elicit a major histocompatibility complex (MHC) class 1 response.
2. The method of claim 1 , wherein the antibody protein comprises a heterologous Fab fragment.
3. The method of claim 2 , wherein the Fab fragment is non-human.
4. The method of claim 3 , wherein the Fab fragment is from mouse.
5. The method of claim 1 , wherein the heterologous CD8 cytotoxic T cell epitope is a self-epitope.
6. The method of claim 5 , wherein the self-epitope is a tumor epitope.
7. The method of claim 1 , wherein the antibody protein is a monoclonal antibody protein.
8. The method of claim 1 , wherein the antibody protein is administered intramuscularly.
9. The method of claim 1 , wherein the antibody protein is administered intradermally.
10. The method of claim 1 , wherein the antibody protein is administered for the treatment of cancer.
11. The method of claim 1 , wherein the antibody protein is administered to the patient with an adjuvant.
12. A method for stimulating a CD8 cytotoxic T cell response in a human patient, comprising:
substituting a single heterologous CD8 cytotoxic T cell epitope for a complementarity determining region (CDR) of an antibody protein that includes human FcγI, the CDR having similar size and charge as the epitope, and the first amino acid downstream of the epitope being chosen from the group consisting of G, K, R, and S; and
administering to the patient a therapeutically effective amount of the antibody protein,
wherein the epitope is cleaved, at its C-terminus, in the proteasome, to thereby elicit a major histocompatibility complex (MHC) class 1 response.
13. The method of claim 12 , wherein the heterologous CD8 cytotoxic T cell epitope is a self-epitope.
14. The method of claim 13 , wherein the self-epitope is a tumor epitope.
15. The method of claim 12 , wherein the therapeutically effective amount of the antibody protein is administered intramuscularly.
16. The method of claim 12 , wherein the therapeutically effective amount of the antibody protein is administered intradermally.
17. The method of claim 12 , wherein the therapeutically effective amount of the antibody protein is administered for the treatment of cancer.
18. The method of claim 12 , wherein the therapeutically effective amount of the antibody protein is administered to the patient with an adjuvant.