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The Ig molecules secreted by these hybrid\u2010hybridomas were fractionated by ion\u2010exchange chromatography, and fractions containing monovalent CD3 antibodies were tested for complement\u2010mediated lysis of T cells. Two monovalent CD3 antibodies with mixed heavy chain isotypes were very poor in lysis but, in contrast, a monovalent antibody possessing two identical rat \u03b3<jats:sub>2b<\/jats:sub> heavy chains but two non\u2010identical light chains was found to be more lytic with human complement than the parental bivalent CD3 antibody. The difference in lysis was not readily explicable in terms of a difference in complement activation at the level of C1q binding or cell\u2010associated C3. A highly purified batch of this lytic monovalent CD3 antibody was prepared in a form suitable for <jats:italic>in vivo<\/jats:italic> therapy. In a preliminary clinical study in one patient with a T lymphoma in leukemic phase this monovalent CD3 antibody was found to be very effective in depleting CD3 tumor cells in the peripheral blood and bone marrow. The cells in the peripheral blood were completely cleared and there was no evidence for antigenic modulation. In addition the antibody was able to reverse cell\u2010mediated kidney rejection in three kidney graft patients. These results suggest that monovalent antibody may be effective <jats:italic>in vivo<\/jats:italic> as well as <jats:italic>in vitro<\/jats:italic> and that a fuller clinical evaluation is justified.<\/jats:p>","DOI":"10.1002\/eji.1830190224","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T10:41:59Z","timestamp":1172745719000},"page":"381-388","source":"Crossref","is-referenced-by-count":32,"title":["The improved lytic function and <i>in vivo<\/i> efficacy of monovalent monoclonal CD3 antibodies"],"prefix":"10.1002","volume":"19","author":[{"given":"Mike","family":"Clark","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol","family":"Bindon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Dyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Friend","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoff","family":"Hale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Cobbold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy","family":"Calne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herman","family":"Waldmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,12,5]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/233527a0"},{"key":"e_1_2_1_3_2","first-page":"13","volume":"42","author":"Gordon J.","year":"1981","journal-title":"Immunology"},{"key":"e_1_2_1_4_2","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.4049\/jimmunol.125.4.1506","volume":"125","author":"Ritz J.","year":"1980","journal-title":"J. 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