The Science of nfP2X7

side view nfP2X7a valuable new oncology target

Biosceptre has shown that nfP2X7 is widely expressed on over 20 types of cancer which together account for approximately 95% of all cancers diagnosed. Biosceptre has developed diagnostics and therapeutics that target nfP2X7 selectively, as it occurs on cancer cells. These include the lead monoclonal antibody candidate BIL03s, an immunohistochemistry diagnostic tool, BPM09, a therapeutic vaccine BIL06v and a topical antibody formulation BIL010t, for treatment of non-melanoma skin cancers. These therapeutics can be used on their own or potentially in combination with other oncology therapeutics.

nfP2X7 is a cancer-specific form of the P2X7 ion channel that is located on the surface of some normal cells. P2X7 is a ligand gated ion channel, consisting of three identical protein subunits. In response to high concentrations of extracellular ATP, P2Xforms a channel driving a range of diverse physiological functions including proliferation and immune cell functions. In response to prolonged ATP stimulation, at concentrations present routinely in the tumour micro environment, P2Xcan form a membrane pore that is associated with induction of cell death. However published data also strongly links P2Xto cancer cell survival and metastatic potential (reviewed, Di Virgilio F, Adinolfi E. Oncogene. 2017;36(3):293-303.).

Dr Barden, a Biosceptre founder, proved that the structure of P2X7 can be modified in cancer to block P2X7 from forming the pore that drives cell death, and thus protecting cells from ATP induced death. This enables cancer cells to survive in the tumour micro environment where high and sustained levels of ATP would otherwise kill cells expressing fully functional P2X7. This conformationally distinct receptor identified by Biosceptre is termed nfP2X7 (non-functional P2X7), since pore function is lost. However, Biosceptre has shown that nfP2X7 retains critical signalling capabilities that support cancer cell survival. Due to its modified conformation, nfP2X7 possesses novel epitopes, normally buried within the structure of functional P2X7, that are visible and available for antibody binding. Targeting cancer cells via these nfP2X7 epitopes delivers great precision and is the basis of Biosceptre’s technology since antibodies targeting these epitopes cannot bind to fully functional P2X7 on normal cells and tissues.

Published Papers & Presentations

ATP in the tumour microenvironment drives expression of nfP2X7, a key mediator of cancer cell survival, SM Gilbert, CJ Oliphant, S. Hassan, AL Peille, P. Bronsert, S. Falzoni, F. Di Virgilio, S. McNulty & R. Lara

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