Methods and compositions for treating cancer with cancer-targeted adjuvants
Here, the inventors describe methods and compositions for targeting a TLR agonist to the tumor cell or stroma. Aspects of the disclosure relate to a polypeptide comprising a tumor targeting agent operatively linked to p(Man-TLR). Also disclosed are compositions and methods for treating cancer in a subject comprising administration of the polypeptide comprising the tumor targeting agent linked to p(Man-TLR) to the subject.
1 . A method for treating cancer, for targeting a TLR agonist to a tumor in a subject, or for increasing the accumulation of a TLR agonist in a tumor in a subject, the method comprising administering a polypeptide comprising a collagen binding domain covalently linked to p(Man-TLR7), wherein the collagen binding domain comprises:
the amino acid sequence of one of SEQ ID NOS: 1, 2, or 8.
2 . The method of claim 1 , wherein the subject has cancer.
3 . The method of claim 1 , wherein the cancer comprises melanoma, lymphoma, bladder, breast, mammary carcinoma, or colon cancer.
4 . The method of claim 3 , wherein the cancer comprises melanoma, breast cancer, or a mammary carcinoma.
5 . The method of claim 1 , wherein the polypeptide or composition is administered systemically, by intravenous injection, intratumorally, or peritumorally.
6 . The method of claim 1 , wherein the polypeptide is further covalently linked to an albumin molecule, wherein the albumin molecule comprises an amino acid sequence having at least 95% sequence identity to one of SEQ ID NOs: 11-14.
7 . The method of claim 1 , wherein the molar ratio of the tumor targeting agent to p(Man-TLR) is 1:5.
8 . The method of claim 1 , wherein the polypeptide is further covalently linked to an albumin molecule, wherein the albumin molecule comprises the amino acid sequence of one of SEQ ID NOs: 11-14.
9 . The method of claim 1 , wherein the cancer comprises a solid tumor.
10 . A method for treating melanoma in a subject, the method comprising administering a polypeptide comprising a collagen binding domain covalently linked to p(Man-TLR7), wherein the collagen binding domain comprises the amino acid sequence of one of SEQ ID NOS: 1, 2, or 8.
11 . The method of claim 10 , wherein the polypeptide is further covalently linked to an albumin molecule and wherein the albumin molecule comprises the amino acid sequence of one of SEQ ID NOs: 11-14.