Antibody-drug conjugates targeting CLEC14A

• CLEC14A is a novel tumour endothelial marker whose expression is highly restricted to tumour endothelial cells.
• Specific anti-CLEC14A antibodies have been developed and shown to localise primarily to tumour tissues.
• In vivo proof of concept experiments with CLEC14A antibody-drug conjugate (ADC) constructs show reduced vascularisation, correlating with decreased tumour burden.
• The comprehensive IP package of three patents covers the anti-CLEC14A antibodies and also various methods for targeting CLEC14A to treat cancer and other diseases.

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 that often co-occur with cancer. 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 tissues.

CLEC14A-targeted treatments are expected to be more efficacious than other vasculature targeting agents (e.g. Avastin), as they act as vasculature disrupting agents on existing and newly formed blood vessels, eradicating tumour vasculature that expresses the protein. 

The distinction from angiogenesis targeting agents such as Avastin is that CLEC14A-targeting agents block neo-angiogenesis by inhibiting VEGF-A, but they do not eradicate established tumour vasculature. Researchers at the University of Birmingham have now developed antibody-drug conjugates that cause endothelial cell cytotoxicity in vitro, disrupting established tumour vasculature and decreasing tumour burden in mice with Lewis lung carcinoma. These antibody-drug conjugates targeting CLEC14A represent promising potential therapies for solid tumours.