BTNL9 and ERMAP as novel inhibitors of the immune system for immunotherapies
Provided are methods of treating a tumor in a subject with a BTNL9-binding antibody. Also provided are methods of treating a tumor in a subject with an ERMAP-binding antibody. A fusion protein comprising a BTNL9 or ERMAP and related compositions and encoding nucleic acids are also provided.
1. A method of treating a tumor in a subject, comprising administering to the subject a therapeutically effective amount of a polypeptide comprising an isolated plasma-soluble polypeptide comprising a soluble portion of short form BTNL2 having the amino acid sequence set forth in SEQ ID NO: 4 and excluding the amino acid sequence set forth in SEQ ID NO: 3, wherein the polypeptide treats the tumor.
2. The method of claim 1 , wherein the tumor is a tumor of a breast, lung, thyroid, melanoma, pancreas, ovary, liver, bladder, colon, prostate, kidney, esophagus, or is a hematological tumor, or wherein the tumor is a lymphoid organ tumor.
3. The method of claim 1 , wherein the isolated plasma-soluble polypeptide is a fusion protein.
4. The method of claim 3 , wherein the fusion protein comprises an Fc portion of an immunoglobulin G.
5. A method of treating an autoimmune disease in a subject, comprising administering to the subject a therapeutically effective amount of an isolated plasma-soluble polypeptide comprising a soluble portion of short form BTNL2 having the amino acid sequence set forth in SEQ ID NO: 4 and excluding the amino acid sequence set forth in SEQ ID NO: 3, wherein the polypeptide treats the autoimmune disease in the subject.
6. The method of claim 5 , wherein the plasma-soluble polypeptide is a fusion protein.
7. The method of claim 6 , wherein the fusion protein comprises an Fc portion of immunoglobulin G.
8. The method of claim 7 , wherein the Fc portion of immunoglobulin G is fused to the soluble portion of BTNL2.
9. An isolated chimeric nucleic acid encoding the polypeptide of claim 1 .
10. An isolated chimeric nucleic acid comprising a first set of nucleotides which encode a soluble portion of short form BTNL2 having the amino acid sequence set forth in SEQ ID NO: 4 and excluding the amino acid sequence set forth in SEQ ID NO: 3.
11. The isolated chimeric nucleic acid of claim 10 , further comprising a second set of nucleotides which encode an Fc portion of an immunoglobulin G.
12. The isolated chimeric nucleic acid of claim 11 , wherein the Fc portion of immunoglobulin G lacks a C-terminal lysine.
13. The isolated chimeric nucleic acid of claim 12 , wherein the second set of nucleotides is recombinantly engineered to encode the Fc portion of immunoglobulin G lacking a C-terminal lysine.
14. The isolated chimeric nucleic acid of claim 11 , wherein the first set of nucleotides and the second set of nucleotides are disposed sequentially within the isolated chimeric nucleic acid.
15. The isolated chimeric nucleic acid of claim 14 , wherein the first set of nucleotides and the second set of nucleotides encode a fusion protein.