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CLEC14A

Overview: 
  • Novel tumour endothelial marker: CLEC14A-specific technologies targeting tumour vasculature
  • Expression is highly restricted to tumour endothelial cells
  • CLEC14A KO mice and in house generated murine monoclonal antibodies demonstrate in vivo tumour burden reduction and inhibition of invasion
  • In vivo POC with specific antibody-drug conjugate therapies (ADC) constructs reduce CLEC14a expressing vascularisation, correlating with reduced tumour burden
  • In vivo POC with specific CAR-T constructs reduce CLEC14a expressing vascularisation, correlating with reduced tumour burden
  • MHRA-approved safety profile of CLEC14A as a target
  • CLEC14A CAR-T preclinical safety profile reviewed by MHRA
  • Comprehensive IP package around the target and the antibodies encompassing three patent applications
The Opportunity: 

CRUK is seeking an industry partner for co-development and/or exclusive licensing of its CLEC14A IP, materials and know-how, to progress anti-CLEC14A antibodies into first-in-human clinical studies.

The Technology: 

Further details around this programme are provided in the slide deck below. In terms of intellectual property: 1) CRUK has filed a patent application (WO2011/027132; priority date: September 2009) describing the potential of CLEC14A as a suitable target for vascular targeting and anti-angiogenesis approaches, which has been granted; 2) a second patent application (WO2016GB50134 20160121; priority date: January 2015) was filed claiming mechanism of action by blocking co-activator function and therapeutic potential between specific Abs (1,4,5) based on unique epitope recognition; 3) the third patent application (WO2017GB50689 20170314, priority date March 2016) claims novel function and therapeutic potential ofspecific Abs, based on unique epitope recognition.

Scientific Background: 

Tumour endothelial markers (TEMs) that are highly expressed in human tumour vasculature compared with vasculature in normal tissue hold clear therapeutic potential. C-type lectin CLEC14A is a novel TEM, a transmembrane protein that is specifically expressed on the surface of tumour endothelial cells and is absent or expressed at a low level on healthy tissues and on non-tumour diseased tissues often co-occurring with cancer. CLEC14A treatments are expected to be more efficacious than other vasculature targeting agents (e.g. avastin) as they act as vasculature disruptive agents on existing and newly formed blood vessels, eradicating tumour vasculature expressing the protein. The distinction from angiogenesis targeting agents, such as the VEGF/VEGF-R inhibitor Avastin, is these agents block neo-angiogenesis by inhibiting VEGF-A, but they do not eradicate established tumour vasculature. Extensive immunohistochemical data demonstrates that CLEC14A is strongly and specifically overexpressed on the tumour vasculature in a wide range of tumours tested, in contrast to vessels of the corresponding normal tissue.

Researchers: 

Professor Roy Bicknell, director of Institute of Cardiovascular Sciences and Professor of functional genetics and Dr. Steven Lee, Senior Research Fellow at University of Birmingham

References: 

Mura M et al; Identification and angiogenic role of the novel tumor endothelial marker CLEC14A. Oncogene. 2011 Jun 27

Rho SS et al; Clec14a is specifically expressed in endothelial cells and mediates cell to cell adhesion. Biochem Biophys Res Commun. 2011 Jan 7

Noy PJ et al; Blocking CLEC14A-MMRN2 binding inhibits sprouting angiogenesis and tumour growth. Oncogene. 2015 Mar 9

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