TMIGD2 AND ITS DERIVATIVES AS BLOCKERS OR BINDERS OF CANCER-EXPRESSED HHLA2 FOR IMMUNOTHERAPIES
Provided are methods of treating an HHLA2-bearing tumor in a subject with a fusion protein comprising an IgV-like domain of a TMIGD2 sufficient to treat the HHLA2-bearing tumor. A fusion protein comprising an IgV-like domain of a TMIGD2 and related compositions and encoding nucleic acids are also provided.
1 . A method of treating an HHLA2-bearing tumor in a subject comprising administering to the subject an amount of a fusion protein comprising an IgV-like domain of a TMIGD2 sufficient to treat the HHLA2-bearing tumor.
2 . The method of claim 1 , wherein the fusion protein comprising an IgV-like domain of a TMIGD2 comprises an Fe portion of an immunoglobulin G.
3 . The method of claim 1 , wherein the C-terminal residue of the IgV-like domain of a TMIGD2 of the fusion protein is fused via a peptide bond to an N-terminal residue of an Fe portion of an immunoglobulin G.
4 . The method of claim 2 , wherein the immunoglobulin G has the sequence of a human immunoglobulin G.
5 . The method of claim 2 , wherein the immunoglobulin G 1s an immunoglobulin G 1.
6 . A method of treating an HHLA2-bearing tumor in a subject comprising administering to the subject an amount of an agent comprising an IgV-like domain of a TMIGD2 conjugated to a cytotoxic agent, and/or administered in combination with radiation therapy, sufficient to treat the HHLA2-bearing tumor.
7 . The method of claim 1 , wherein the IgV-like domain of a TMIGD2 comprises consecutive amino acid residues having the sequence set forth in SEQ ID NO:3.
8 . A method of inhibiting immunosuppression in a subject by an HHLA2-bearing tumor comprising administering an amount of (i) a fusion protein, comprising an IgV-like domain of a TMIGD2 and an Fe portion of an immunoglobulin G, or (ii) an amount of a purified protein comprising an IgV-like domain of a TMIGD2 but not comprising SEQ ID N0:4, sufficient to inhibit immunosuppression in a subject by an HHLA2-bearing tumor.
9 . The method of claim 1 , wherein the HHLA2 of the HHLA2-bearing tumor is a human HHLA2.
10 . The method of claim 1 , wherein the HHLA2-bearing tumor is a tumor of a breast, lung, thyroid, melanoma, pancreas, ovary, liver, bladder, colon, prostate, kidney, or esophagus, or is a hematological tumor.
11 . The method of claim 10 , wherein the HHLA2-bearing tumor is a hematological tumor and is a leukemia or a lymphoma.
12 . The method of claim 10 , wherein the HHLA2-bearing tumor is a tumor of the breast and is a triple negative breast cancer.
13 . The method of claim 1 , wherein the fusion protein comprises consecutive amino acid residues having the sequence set forth in SEQ ID N0:2.
14 . The method of claim 1 , wherein the fusion protein comprises consecutive amino acid residues having the sequence set forth in SEQ ID N0:3.
15 . An isolated fusion protein comprising an IgV-like domain of a TMIGD2 and an Fc portion of an immunoglobulin G, wherein the isolated fusion protein comprises SEQ ID NO:2 or SEQ ID NO:3.
16 . The isolated fusion protein of claim 15 , comprising SEQ ID NO:2.
17 . The isolated fusion protein of claim 15 , comprising SEQ ID NO:3.
18 . An isolated chimeric nucleic acid encoding the isolated fusion protein of claim 15 .
19 . A composition comprising the isolated fusion protein of claim 15 and a carrier.
20 . The composition of claim 19 , which is a pharmaceutical composition, and wherein the carrier is a pharmaceutical carrier.