3094 Background: P2X7 receptor, a ligand-gated channel, is activated by extracellular ATP and mediates ATP induced apoptosis. Several polymorphisms leading to loss of function of P2X7 have been described. Overexpression of non-functioning P2X7 receptor (nfP2X7), able to form a Ca2+channel but not an apoptotic pore, is found on every type of cancer cell but no normal cells, making it a perfectly selective target for immune therapy approaches. Methods: Samples from various tumor types were analyzed for the expression of nfP2X7 using immunohistochemistry. MoDC from n=6 patients with advanced metastatic sarcoma (2 osteosarcoma, 4 soft tissue sarcoma) with disease progression after failure of extensive standard therapies were primed against the nfP2X7using a specific peptide. MoDC were harvested, analyzed by flow cytometry and applied to the patient intradermaly. Specific T-cell response was analyzed by IFN-gamma Elispot. Results: nfP2X7 is overexpressed in essentially all analyzed tumor samples from all cell types: epithelial, mesenchymal, neural, germinal examined in large numbers (n = 5 to >1,000). The uniquely displayed epitope associated with the ATP binding site exposed on nfP2X7 but hidden in P2X7 was found on the cancer cell surface but not on the surface of any normal cells. MoDC primed with a specific peptide against nfP2X7 show a distinct DC morphology and an up-regulation of the maturation marker CD83. Patients are 6-9 months (onset June 2012) under treatment at time of abstract submission. 2 patients have a disease stabilization. One further patient with a metastatic, rapidly growing osteosarcoma showed a mixed response. IFN-gamma Elispot, which was exemplarily performed, shows a nfP2X7-specific T-cell response. Conclusions: Efficient inductions of an antitumor response by dendritic cell therapy require the definition and choice of an optimal target, being expressed in almost all kinds of tumors. nfP2X7, a set of non-functioning forms of the P2X7 receptor unable to initiate apoptosis but maintaining channel activity, could therefore be an optimal universal candidate. The efficacy of dendritic-cell based therapy may be improved by priming the MoDC against nfP2X7 and thus may improve the clinical outcome.
Anticancer property of hexane extract of Suaeda fruticose plant leaves against different cancer cell lines