A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 39/395 (2006.01) A61K 31/164 (2006.01) A61K 31/337 (2006.01) A61K 31/555 (2006.01) A61K 31/704 (2006.01) A61K 38/02 (2006.01) A61K 38/17 (2006.01) A61K 38/19 (2006.01) A61K 38/44 (2006.01) A61K 45/00 (2006.01) A61P 35/00 (2006.01) A61P 37/04 (2006.01) G01N 33/50 (2006.01) G01N 33/543 (2006.01) G01N 33/68 (2006.01)
Patent
CA 2665771
Anthracyclines-treated tumor cells are particularly effective in eliciting an anti-cancer immune response, where the rDNA-damaging agents, such as etoposide and mitomycin C do not induce immunogenic cell death. Anthracyclines induce the rapid, pre-apoptotic translocation of calreticulin (CRT) and/or ERP57 to the cell surface. Knock down of CRT and/or ERP57 suppressed the phagocytosis of anthracyclines-treated tumor cells by dendritic cells and abolished their immunogenicity in mammals, such as mice. The anthracyclines-induced CRT and/or ERP57 translocation was mimicked by inhibition of the protein phosphatase1/GADD34 complex. Administration of recombinant calreticulin, and not recombinant ERP57, or inhibitors of protein phosphatase1/GADD34 restored the immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced their antitumor effects in vivo. These data identify calreticulin and/or ERP57 as a key feature determining anti-cancer immune responses and delineate a possible strategy for immunogenic chemotherapy. This invention demonstrates that calreticulin exposure dictates also sperm-egg fusion. This invention includes also the using of recombinant CRT and/or ERP57 or the inducers of the translocation of CRT and/or ERP57 protein to treat sterility. The detection of the translocation of CRT and/or ERP57 is a good way to screen new immunogenic molecules and compounds.
Obeid Michel S.
Na
Obeid Michel S.
LandOfFree
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