Background / Context / Abstract:

Dickkopf1 (DKK1) is a secretory protein that antagonizes oncogenic Wnt signalling by binding to the Wnt coreceptor low density lipoprotein receptor–related protein 6 (LRP6). 
It has been shown to suppress tumorigenesis in some cancer cells, however, it is also up-regulated in many types of cancer and associated with poor prognosis. 
Wnt-independent mechanisms by which DKK1 promotes cancer cell proliferation are not well understood.
In this study, researchers identified that cytoskeleton-associated protein 4 (CKAP4) is a novel DKK1-binding protein by using mass spectrometry analyses and immune sedimentation, then found that it becomes a new therapeutic target. 
CKAP4 was detected in tumor lesions of 66–74% of pancreatic and lung cancer cases. 
The researchers also demonstrated that DKK1 interacts with CKAP4 to promote activation of AKT, and CKAP4 specifically regulate tumor cell proliferation by DKK1. 
They also showed that suppressing of CKAP4 gene expression or polyclonal antibodies inhibit proliferation of tumor cells.

Technology Overview:

Lung, pancreatic and some other cancer treatment by using anti-CKAP4 mAb.  According to the fact that DKK1/CKAP4 signalling promotes cancer cell proliferation, highly tumour suppressing effects are expected at cancer describe above harbouring with DKK1 over-expression and high expression of CKAP4 on its cell membrane.

Benefits:

Advantages:

-　Some anti-CKAP4 monoclonal antibodies (mAbs) obtained
–  Tumor suppressing effects were found for both pancreatic and lung cancer in mouse xenograft model by using anti-CKAP4 mAbs

Potential Applications / Potential Markets:

Anticancer drugs (antibody drugs)

State of Development / Opportunity / Seeking:

・Available for exclusive and non-exclusive licensing
・Exclusive/non-exclusive evaluation for defined period (set up for options)
・Collaborative/supportive research

IP Status:

1. WO 2016/136372(National phase: EP, CN and Issued: JP,US,CA)
2. WO2019/065747A1(National phase: JP,CA,CN,EP,US)

Figures:

Fig. 1 | Antiproliferative effect of anti-CKAP4 antibody on DKK1- and CKAP4-expressing cancer cells.
S2-CP8 cells (pancreatic cancer) and A549 cells (lung cancer) were implanted by s.c. into immunodeficient mice.  Polyclonal anti-CKAP4 antibodies (A, B), and Monoclonal anti-CKAP4 antibodies (C) were injected by i.p. twice per week.

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