Dickkopf2 (dkk2) inhibition suppresses tumor formation

Abstract

The present invention relates to the discovery that inhibition of Dickkopf2 (DKK2) increases CD8+ cytotoxic T lymphocyte (CTL) activity, attenuates tumor angiogenesis, and hence suppresses tumor formation. Thus, in various embodiments described herein, the methods of the invention relate to methods of treating cancer by administering to a patient an effective amount of DKK2 gene depleting agent, methods for providing anti-tumor immunity and anti-tumor angiogenesis in a subject, methods of stimulating a T cell mediated immune response to a cell population or a tissue and suppressing tumor angiogenesis in a subject. Additionally, the current invention includes methods of diagnosing a cancer or a predisposition of developing a cancer or a metastasis and methods for determining the use of immunotherapy treatment or cancer vaccine for treating cancer. Furthermore, the invention encompasses a pharmaceutical composition for treating cancer as well as a kit for carrying out the aforementioned methods.

What is claimed: 
     
         1 . A pharmaceutical composition comprising a DKK2 depleting agent and a pharmaceutically acceptable carrier. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the DKK2 depleting agent possesses neutralizing activity. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the DKK2 depleting agent is selected from the group consisting of a DKK2 antibody, siRNA, ribozyme, an antisense molecule, an aptamer, a peptidomimetic, a small molecule, and a combination thereof. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the DKK2 depleting agent is an antibody and the antibody is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a humanized antibody, a synthetic antibody, a heavy chain antibody, a human antibody, a biologically active fragment of an antibody, an antibody mimic and any combination thereof. 
     
     
         5 . The pharmaceutical composition of  claims 4 , wherein the DKK2 antibody targets a DKK2 neutralizing epitope that comprises at least one of the amino acid sequences selected from the group consisting of SEQ ID NOs: 1, 5 and 7. 
     
     
         6 . The pharmaceutical composition of  claim 4 , wherein the DKK2 antibody is a synthetic antibody comprising at least one of the amino acid sequences selected from the group consisting of YAL008-5-1A10 (SEQ ID NOs 8 and 9), YAL008-1-5F8 (SEQ ID NOs 10 and 11), and YAL008-7-1A10 (SEQ ID NOs 12 and 13). 
     
     
         7 . The pharmaceutical composition of  claim 1 , comprising an additional agent selected from the group consisting of a chemotherapeutic agent, an anti-cell proliferation agent, an immunotherapeutic agent and any combination thereof. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the additional agent is a programmed cell death 1 (PD-1) antibody.