{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T09:13:29Z","timestamp":1717060409752},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T00:00:00Z","timestamp":1172793600000},"content-version":"vor","delay-in-days":4443,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[1995,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have investigated the cytotoxic performance of two different anti\u2010CD7\/anti\u2010saporin BsAb's (HB2 \u00d7 DB7\u201018 and Q1.1), three anti\u2010CD38\/anti\u2010saporin BsAb's (OKT10 \u00d7 RabSap, OKT10 \u00d7 DB7\u201018 and Q4.1) and an anti\u2010CD7 (HB2\u2010Sap) and anti\u2010CD38\u2010saporin (OKT10\u2010Sap) immunotoxin for delivering the ribosome inactivating protein (rip) to the human T\u2010cell acute lymphoblastic leukemia cell line HSB\u20102. In the case of CD7 as target molecule the immunotoxin outperformed both anti\u2010CD7 BsAb's being six times more effective than HB2 \u00d7 DB7\u201018 and 98 times more so than Q1.1 at effectively inhibiting protein synthesis in a dose dependent manner. The chemically constructed HB2 \u00d7 DB7\u201018 BsAb was more effective at inhibiting protein synthesis and cell growth in target HSB\u20102 cells in a dose dependent manner than the quadroma produced BsAb Q1.1. Both BsAb demonstrated a prozone effect used at concentrations above 0.1 nM though this was more pronounced for Q1.1 than for HB2 \u00d7 DB7\u201018. The prozone effect was partially though not completely reversed by increasing the concentration of saporin in the system. In the case of CD38 as target molecule the anti\u2010CD38 IT OKT10\u2010Sap performed poorly, never actually achieving its IC<jats:sub>50<\/jats:sub>. Two BsAb's constructed with monoclonal anti\u2010saporin Fab arms each recognizing a different epitope on the saporin molecule also performed poorly. IN contrast the BsAb OKT10 \u00d7 RabSap constructed with Fab derived from a rabbit polyclonal anti\u2010saporin antiserum performed in a dose dependent manner achieving its IC<jats:sub>50<\/jats:sub> at a concentration of 1.3 nM. This BsAb also exhibited a prozone effect. These results exemplify the importance of cross linking adjacent target molecules on the cell surface in order to achieve effective delivery of saporin to the cell interior.<\/jats:p>","DOI":"10.1002\/hon.2900130403","type":"journal-article","created":{"date-parts":[[2007,2,19]],"date-time":"2007-02-19T16:51:20Z","timestamp":1171903880000},"page":"185-200","source":"Crossref","is-referenced-by-count":10,"title":["Comparison of the performance of anti\u2010CD7 and anti\u2010CD38 bispecific antibodies and immunotoxins for the delivery of saporin to a human T\u2010cell acute lymphoblastic leukemia cell line"],"prefix":"10.1002","volume":"13","author":[{"given":"David J.","family":"Flavell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sue","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiko","family":"Okayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loretta","family":"Emery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sopsamorn U.","family":"Flavell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,3,2]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00205450"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00205591"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1990.115"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199308123290703"},{"key":"e_1_2_1_6_2","first-page":"151","article-title":"An immunotoxin composed ofmonoclonal anti\u2010Thy 1.1 antibody and a ribosome\u2010inactivating protein from Saponaria officinalis: potent antitumor effects in vitro and in vivo","volume":"75","author":"Thorpe P. 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Immunol."},{"key":"e_1_2_1_17_2","first-page":"1393","article-title":"T\u2010cell killing of target cells induced by hybrid antibodies: Comparison of two bispecific antibodies","volume":"79","author":"Clark M. R.","year":"1987","journal-title":"J. Natl Cancer Inst."},{"key":"e_1_2_1_18_2","doi-asserted-by":"crossref","first-page":"12035","DOI":"10.1016\/S0021-9258(17)38981-0","article-title":"Purified immunotoxins that are reactive with human lymphoid cells","volume":"260","author":"Lambert J. M.","year":"1985","journal-title":"J. Biol. Chem."},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1994.52"},{"key":"e_1_2_1_20_2","doi-asserted-by":"crossref","unstructured":"Flavell D. J. Boehm D. Emery L. Noss A. Ramsay A. Flavell S. U.Therapy of human B\u2010cell lymphoma bearing SCID mice is more effective with anti\u2010CD19 and anti\u2010CD38\u2010saporin immunotoxins used in combination than with either immunotoxin used alone.Int. J. 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