Purinergic (P2X) receptors are ATP-gated cation-selective channels. Each receptor is made up of three protein subunits or monomers. To date seven separate genes encoding P2X monomers have been identified: P2X1, P2X2, P2X3, P2X4, P2X5, P2X6, P2X7.
P2X7 receptors are of particular interest as the expression of these receptors is understood to be limited to cells having potential to undergo programmed cell death, such as thymocytes, dendritic cells, lymphocytes, macrophages and monocytes. There is some expression of P2X7 receptors in normal homeostasis, such as on erythrocytes.
Interestingly, a P2X7 receptor containing one or more monomers having a cis isomerisation at Pro210 (according to SEQ ID NO: 1 in FIG. 1) and which is devoid of ATP binding function has been found on cells that are understood to be unable to undergo programmed cell death, such as preneoplastic cells and neoplastic cells.
Antibodies generated from immunisation with a peptide including Pro210 in cis bind to 20 P2X7 receptors that are devoid of ATP binding function. However, they do not bind to P2X7 receptors capable of binding ATP. Accordingly, these antibodies are useful for selectively detecting many forms of carcinoma and haemopoietic cancers and to treatment of some of these conditions.
The region of the P2X7 receptor containing Pro210 forms part of the extra cellular 25 domain of the receptor. Antibodies raised against other epitopes on this domain, including those that bind regions including from VaI71 to Va187 (according to SEQ ID NO: 1 in FIG. 1) and from Lys 137 to Cys152 (according to SEQ ID NO:1 in FIG. 1) have been found not to be capable of selectively binding to the receptor that is devoid of ATP binding function. Hence, other than the antibodies directed to the region including Pro210, no other antibodies have been found to date to be able to discriminate between 5 ATP and non ATP binding receptors.
There is a need for reagents for detection of cancer and in this context, for new antibodies capable of discriminating between ATP and non ATP binding P2X7 receptors. There is also a need for new cancer therapeutics, including antibodies and immunogens for providing an anti tumour response.
USPTO Backgrounds
USPTO Backgrounds