Methods for modulating an immune response
The present disclosure provides methods of modulating an immune response in an individual. The present disclosure provides methods of treatment. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) and an immune checkpoint inhibitor to an individual. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) to an individual who is undergoing treatment with immune checkpoint inhibitor.
1. A method of treating an individual having a cancer that expresses an HPV16 E7 antigen, the method comprising administering to the individual a combination of (i) an effective amount of an immune checkpoint inhibitor that targets PD-1, wherein the immune checkpoint inhibitor comprises pembrolizumab, and (ii) an effective amount of a protein that is a homodimer of two multimeric polypeptides, wherein each multimeric polypeptide comprises:
a) a first polypeptide comprising from N-terminus to C-terminus:
i) an HPV16 E7 epitope comprising amino acid sequence YMLDLQPETT (SEQ ID NO:77);
ii) a linker comprising amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO:207); and
iii) a β2-microglobulin (β2M) polypeptide comprising the amino acid sequence set forth in SEQ ID NO:48; and
b) a second polypeptide comprising two variant IL-2 polypeptides, a class I MHC heavy chain polypeptide, and a variant immunoglobulin Fc polypeptide, wherein the second polypeptide comprises the amino acid sequence set forth in SEQ ID NO:36,
wherein the first and second polypeptides are covalently linked to one another via a disulfide bond between the Cys residue at amino acid 12 of the β2M polypeptide and the Cys residue at amino acid 236 of the class I MHC heavy chain polypeptide, and
wherein the multimeric polypeptides are joined to each other by one or more disulfide bonds that join the variant immunoglobulin Fc polypeptide of one multimeric polypeptide to the variant immunoglobulin Fc polypeptide of the other multimeric polypeptide, and
wherein the immune checkpoint inhibitor and the protein are administered at the same time or at different times.
2. A method according to claim 1 , wherein the cancer is a head and neck cancer, a cervical cancer, or a genitoanal cancer.
3. A method according to claim 1 , wherein the individual has become refractory to a prior treatment for the cancer.
4. A method according to claim 2 , wherein the individual has become refractory to a prior treatment for the cancer.
5. A method according to claim 1 , wherein the individual has failed to respond to a prior treatment for the cancer.
6. A method according to claim 2 , wherein the individual has failed to respond to a prior treatment for the cancer.
7. A method according to claim 1 , wherein the protein is administered in an amount of 100 μg to 1 mg per kg of body weight.
8. A method according to claim 1 , wherein the protein is administered in an amount of 1-5 mg per kg of body weight.
9. A method according to claim 1 , wherein the protein is administered in an amount of 5-10 mg per kg body weight.
10. A method according to claim 1 , wherein the protein is administered in an amount of 10-15 mg per kg body weight.
11. A method according to claim 1 , wherein the protein is administered in an amount of 15-20 mg per kg body weight.
12. A method according to claim 2 , wherein the protein is administered in an amount of 100 μg to 1 mg per kg of body weight.
13. A method according to claim 2 , wherein the protein is administered in an amount of 1-5 mg per kg of body weight.
14. A method according to claim 2 , wherein the protein is administered in an amount of 5-10 mg per kg body weight.
15. A method according to claim 2 , wherein the protein is administered in an amount of 10-15 mg per kg body weight.
16. A method according to claim 2 , wherein the protein is administered in an amount of 15-20 mg per kg body weight.