{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T12:35:23Z","timestamp":1759581323188},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,3,18]],"date-time":"2014-03-18T00:00:00Z","timestamp":1395100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2014,9,15]]},"abstract":"<jats:p>CMML (chronic myelomonocytic leukemia) belongs to the group of myeloid neoplasms known as myelodysplastic and myeloproliferative diseases. In some patients with a history of CMML, the disease transforms to acute myelomonocytic leukemia (AMML). There are no specific treatment options for patients suffering from CMML except for supportive care and DNA methyltransferase inhibitors in patients with advanced disease. New treatment strategies are urgently required, so we have investigated the use of immunotherapeutic directed cytolytic fusion proteins (CFPs), which are chimeric proteins comprising a selective domain and a toxic component (preferably of human origin to avoid immunogenicity). The human serine protease granzyme B is a prominent candidate for tumor immunotherapy because it is expressed in cytotoxic T lymphocytes and natural killer cells. Here, we report the use of CD64 as a novel target for specific CMML and AMML therapy, and correlate CD64 expression with typical surface markers representing these diseases. We demonstrate that CD64\u2010specific human CFPs kill CMML and AMML cells <jats:italic>ex vivo<\/jats:italic>, and that the mutant granzyme B protein R201K is more cytotoxic than the wild\u2010type enzyme in the presence of the granzyme B inhibitor PI9. Besides, the human CFP based on the granzyme B mutant was also able to kill AMML or CMML probes resistant to Pseudomonas exotoxin A.<\/jats:p>","DOI":"10.1002\/ijc.28786","type":"journal-article","created":{"date-parts":[[2014,2,13]],"date-time":"2014-02-13T10:04:04Z","timestamp":1392285844000},"page":"1497-1508","source":"Crossref","is-referenced-by-count":24,"title":["Targeted <i>ex vivo<\/i> reduction of CD64\u2010positive monocytes in chronic myelomonocytic leukemia and acute myelomonocytic leukemia using human granzyme B\u2010based cytolytic fusion proteins"],"prefix":"10.1002","volume":"135","author":[{"given":"Sonja","family":"Schiffer","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine and Immunotherapy Institute for Biomedical Engineering, University Hospital RWTH Aachen Aachen Germany"},{"name":"Department of Pharmaceutical Product Development Fraunhofer IME Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhard","family":"Rosinke","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Product Development Fraunhofer IME Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edgar","family":"Jost","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology (Internal Medicine IV) University Hospital RWTH Aachen  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grit","family":"Hehmann\u2010Titt","sequence":"additional","affiliation":[{"name":"Pharmedartis GmbH Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Huhn","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Immunotherapy Institute for Biomedical Engineering, University Hospital RWTH Aachen Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Melmer","sequence":"additional","affiliation":[{"name":"Pharmedartis GmbH Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Barth","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Immunotherapy Institute for Biomedical Engineering, University Hospital RWTH Aachen Aachen Germany"},{"name":"Department of Pharmaceutical Product Development Fraunhofer IME Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theo","family":"Thepen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Product Development Fraunhofer IME Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,3,18]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"49","volume-title":"World Health Organization Classification of Tumors: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues","author":"Vardiman JW","year":"2001"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-04-1199"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-553X.2010.01251.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.119"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1309\/HRJ1XKTD77J1UTFM"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1999.01431.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800707"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1988.6.9.1417"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10832"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-06-440347"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2013.02.017"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70003-8"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2012.04175.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj080363"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-325050"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2009.01192.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2010.00894.x"},{"key":"e_1_2_7_19_1","first-page":"1341","article-title":"Targeted delivery of human pro\u2010apoptotic enzymes to tumor cells: in vitro studies describing a novel class of recombinant highly cytotoxic agents","volume":"2","author":"Liu Y","year":"2003","journal-title":"Mol Cancer Ther"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801724105"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.7.8.6261"},{"key":"e_1_2_7_22_1","first-page":"349","article-title":"Involvement of granzyme B and perforin gene expression in the lytic potential of human natural killer cells","volume":"32","author":"Clement MV","year":"1990","journal-title":"Nouv Rev Fr Hematol"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209607200"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.11.3781-3794.2000"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200210158"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.43.27934"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80550-6"},{"key":"e_1_2_7_28_1","article-title":"Inhibition of Granzyme B by PI\u20109 protects prostate cancer cells from apoptosis","author":"Ray M","journal-title":"Prostate"},{"key":"e_1_2_7_29_1","first-page":"275","article-title":"Expression of proteinase inhibitor\u20109\/serpinB9 in non\u2010small cell lung carcinoma cells and tissues","volume":"36","author":"Rousalova I","year":"2010","journal-title":"Int J Oncol"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.12.4540"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.1.232"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.24133"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0554"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.49.5.511"},{"key":"e_1_2_7_35_1","first-page":"8414","article-title":"Recombinant CD64\u2010specific single chain immunotoxin exhibits specific cytotoxicity against acute myeloid leukemia cells","volume":"63","author":"Tur MK","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-010-1482-5"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0b013e31816a2d23"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2013.08.005"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R100016200"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2013.4"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161209788923967"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.34"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2005.05869.x"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1089\/152581601750098318"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.5581\/1516-8484.20120058"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08819.x"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.7981"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25766"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2003.11.005"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.461343"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2006.03006.x"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.155.10.4996"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.28786","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.28786","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T19:47:37Z","timestamp":1722109657000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.28786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,18]]},"references-count":51,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,9,15]]}},"alternative-id":["10.1002\/ijc.28786"],"URL":"https:\/\/doi.org\/10.1002\/ijc.28786","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,18]]}}}