The Science of nfP2X7

side view nfP2X7P2X7 is a trans-membrane receptor located on the surface of some normal cells. It is involved in a variety of signalling pathways driving a range of physiological functions including cell death, proliferation and immune cell responses. P2X7 is a ligand gated ion channel formed of three identical protein subunits that function together to form an ion channel in response to high concentrations of extracellular ATP and a large pore in response to prolonged ATP stimulation.

Biosceptres’ key insight is that in cancer, the structure of P2X7 is modified, causing it to lose the ability to form a large molecular weight pore that can drive cell death. This conformationally distinct receptor is defined as nfP2X7 (non-functional P2X7) and Biosceptre has shown it is involved in supporting cancer cell survival and proliferation. In addition, nfP2X7 possesses key epitopes that are available for antibody binding that are not available for binding on P2X7.

Biosceptre has developed antibodies that target precisely these epitopes on nfP2X7 as they occur on cancer cells and our lead monoclonal antibody candidates (including BIL03s) binds to the target in a manner that leads to the death of cancer cells. As well as its lead domain antibody (BIL03s), Biosceptre has applied the science of nfP2X7 to the development of powerful immunohistochemistry  diagnostic tools, to the development of a therapeutic vaccine (BIL06v) and the development of a polyclonal topical antibody formulation (BIL010t) for treatment of non-melanoma skin cancers.

Dr Julian Barden, a Biosceptre founder, demonstrated that nfP2X7 is widely expressed on cancer cells but not on normal tissue. To date, Biosceptre has shown nfP2X7 is present in over 20 types of cancer which together account for approximately 95% of all cancers. Biosceptre has now developed a range of therapeutics and diagnostics that are specific to cancer cells and that can’t bind to normal, functional P2X7. Therefore, nfP2X7 is a novel target for oncology therapy which can be exploited on its own or in combination with other oncology therapeutics. The presence of nfP2X7 on many cancers indicates that Biosceptres’ therapeutic pipeline has great potential application against many forms of cancers.

Published Papers & Presentations

A phase I clinical trial demonstrates that nfP2X7-targeted antibodies provide a novel, safe and tolerable topical therapy for basal cell carcinoma, S.M. Gilbert, A. Gidley Baird, S. Glazer,  J.A. Barden,  A. Glazer , L.C. Teh and J. King

Presentation at Belgrade COST Meeting March 2017

Markers for the development of early prostate cancer, Slater MD, Lauer C, Gidley-Baird A, Barden JA, J Pathol 2003- 199, 368-377

Increased Expression of apoptotic markers in melanoma, Slater M, Scolyer RA, Gidley-Baird A, Thompson JF, Barden JA, Melanoma Research 2003, 13-137 – 145

Genetic Polymorphisms of the Human P2X7 Receptor and Relationship to Function, Wiley JS, Gu BJ, Zhang W, Worthington RA, Dao-Ung P, Shemon AN, Sluyter R, Liang S, Barden JA

Early prostate cancer detected using expression of non-functional cytolytic P2X7 receptors, Slater M, Danieletto S, Gidley-Baird A, Teh LC, Barden JA, Histopathology 2004, 44, 206-215

Differentiation between cancerous and normal hyperplastic lobules in breast lesions, Slater M, Danieletto S, Pooley M, Teh LC, Gidley-Baird A, Barden JA, Breast Cancer Research & Treatment 83- 1-10, 2004

Differentiating keratoacanthoma from squamous cell carcinoma by the use of apoptotic and cell adhesion markers, Slater M, Barden JA, Histopathology 2005, 47, 170-178

Detection of preneoplasia in histologically normal prostate biopsies, Slater MD, Delprado WJ, Murphy CR, Barden JA, Prostate Cancer Prostatic Dis. 2001, 4(2) 92-96

An Ile-568 to Asn Polymorphism Prevents Normal Trafficking and Function to the Human P2X7 Receptor, Wiley JS, Dao-Ung LP, Li C, Semon AN, Gu BJ, Smart ML, Fuller SJ, Barden JA, Petrou S, Sluyter R