Selective targeting of the TREML1/MD2 interaction by small peptide or protein and its use for vaccine adjuvants

1 . A method of boosting an immune response against cancer cells in a subject in need thereof, wherein the method comprises:

administering a pharmaceutical composition comprising a cancer vaccine and a soluble TREM-like transcript-1 (TREML1) to the subject, the soluble TREML1 comprising a TREML1 extracellular domain (ECD) or TREML1 stalk polypeptide; and

inhibiting growth of the cancer cells, wherein the inhibition of the growth of the cancer cells is higher as compared to the pharmaceutical composition comprising the cancer vaccine without the soluble TREML1, thereby boosting an immune response against the cancer cells in the subject.

2 . The method according to claim 1 , wherein the TREML1 ECD or TREML1 stalk polypeptide is obtained from human or mouse TREML1.

3 . The method according to claim 1 , wherein the TREML1 ECD or TREML1 stalk polypeptide comprises the amino-acid sequence of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, or SEQ ID NO:4.

4 . The method according to claim 1 , wherein the pharmaceutical composition further comprises Toll-like receptor (TLR) agonist.

5 . The method according to claim 4 , wherein the TLR agonist is a lipopolysaccharide, a heat shock protein, a fibrinogen, a heparan sulfate fragment, a hyaluronic acid fragment, a CpG oligodeoxynucleotide, 4-amino-2-(ethoxymethyl)-α,α-dimethyl-1H-imidazo[4,5-c]quinoline-1-ethanol (R848), or an opioid drug.

6 . The method according to claim 1 , wherein the cancer vaccine comprises an antigen.

7 . The method according to claim 6 , wherein the antigen is a marker of a cancer.

8 . The method according to claim 7 , wherein the cancer cells are from a cancer selected from the group consisting of colorectal cancer, breast cancer, lung cancer, melanoma, hepatoma, head and neck cancers, squamous cell carcinomas of the lung, ovarian cancer, uterine cancer, prostate cancer, gastric carcinoma, cervical cancer, esophageal carcinoma, bladder cancer, kidney cancer, brain cancer, bone cancer, pancreatic cancer, skin cancer, cutaneous or intraocular malignant melanoma, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, non-Hodgkin's lymphoma, esophagus cancer, small intestine cancer, endocrine system cancer, thyroid gland cancer, parathyroid gland cancer, adrenal gland cancer, sarcoma of soft tissue, urethra cancer, penis cancer, chronic or acute leukemias, solid tumors of childhood, lymphocytic lymphoma, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain stem glioma, pituitary adenoma, Kaposi's sarcoma, epidermoid cancer, squamous cell cancer, medulloblastoma pilomatrixomas, endometrial cancer, multiple myeloma, and T-cell lymphoma.

9 . The method according to claim 8 , wherein the chronic or acute leukemias comprise acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, or chronic lymphocytic leukemia.

10 . The method according to claim 1 , wherein the method enhances an innate immune response in the subject.

11 . The method according to claim 1 , wherein the method enhances an adaptive immune response in the subject.

12 . A method of enhancing a TLR-induced activation of cells, wherein the method comprises;

administering a pharmaceutical composition comprising a TLR agonist and a soluble TREML1 to the cells, the soluble TREML1 comprising TREML1 ECD or TREML1 stalk polypeptide; and

inducing a higher level of TLR-induced activated cells as compared to the pharmaceutical composition comprising the TLR agonist without the soluble TREML1, thereby enhancing a TLR-induced activation of cells.

13 . The method according to claim 12 , wherein the activation comprises activation of monocytes.

14 . The method according to claim 13 , wherein the activation of monocytes comprises secretion of NF-κB or TNF-α.

15 . The method according to claim 12 , wherein the activation of cells comprises dendritic cell maturation.