{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T02:28:43Z","timestamp":1759026523609},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2006,7,17]],"date-time":"2006-07-17T00:00:00Z","timestamp":1153094400000},"content-version":"vor","delay-in-days":4756,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[1993,7,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cross\u2010linking of specific tumor antigens with the T\u2010cell\u2010associated CD3 and CD28 antigens can increase IL\u20102 secretion, proliferation and antigen\u2010specific cytotoxicity in resting T cells. This cross\u2010linking can be achieved effectively by bispecific monoclonal antibodies (BiMAb) with specificity for both the tumor antigen and CD3 or CD28 antigen, respectively. To take advantage of the enhanced activation of CD3 pre\u2010activated T cells by additional activation via the CD28 antigen, BiMAb OKT3\/HRS\u20103 with reactivity to both CD3 and the Hodgkin's\u2010lymphoma\u2010associated CD30 antigen and the BiMAb 15E8\/ HRS\u20103 with reactivity to both CD28 and CD30 antigen were generated by hybridoma fusion. Resting T cells, represented by Jurkat cells (CD3<jats:sup>+<\/jats:sup> \/CD28<jats:sup>+<\/jats:sup>) were specifically activated to produce IL\u20102 by co\u2010cultivation with an EBV\u2010transformed B\u2010cell line (LAZ509, CD30<jats:sup>+<\/jats:sup>\/CD19<jats:sup>+<\/jats:sup>) only in the presence of the CD30\/ CD28 cross\u2010linking BiMAb and an additional cross\u2010linking anti\u2010CD3\/CDI9 BiMAb (OKT3\/6A4). Neither the cross\u2010linking BiMAbs alone nor any combination of the monospecific parental MAbs induced a comparable IL\u20102 production by Jurkat cells in the presence of LAZ509. In addition, using a combination of these BiMAbs, an antigen\u2010dependent cytotoxicity was induced by targeting APC\u2010depleted peripheral blood lymphocytes to CD30<jats:sup>+<\/jats:sup> L540 cells. T cells, previously specifically activated by CD3\/CD30 in the presence of CD30 antigen, were cytotoxic to CD30<jats:sup>+<\/jats:sup> cell lines only after incubation with BiMAb anti\u2010CD28\/ CD30. Neither of the BiMAbs nor any of the parental antibodies induced a comparable effect. Our results indicate that such BiMAbs may offer a new approach for specific immunotherapy of Hodgkin's lymphoma, which takes advantage of cytokine secretion and cytotoxicity of activated T cells.<\/jats:p>","DOI":"10.1002\/ijc.2910540517","type":"journal-article","created":{"date-parts":[[2007,2,19]],"date-time":"2007-02-19T23:32:12Z","timestamp":1171927932000},"page":"820-827","source":"Crossref","is-referenced-by-count":27,"title":["CD30\u2010antigen\u2010specific targeting and activation of T cells via murine bispecific monoclonal antibodies against CD3 and CD28: Potential use for the treatment of hodgkin's lymphoma"],"prefix":"10.1002","volume":"54","author":[{"given":"Christoph","family":"Pohl","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Denfeld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Renner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfram","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heribert","family":"Bohlen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ugur","family":"Sahin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Hombach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9","family":"van Lier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Schwonzen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volker","family":"Diehl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Pfreundschuh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,17]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(89)90188-3"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830190515"},{"key":"e_1_2_1_4_1","unstructured":"Bohlen H. Moldenhauer G. D\u00f6rken B. Diehl V.andTesch H. Lysis of autologous B\u2010CLL cells by cytotoxic T\u2010lymphocytes induced by stimulation with two bispecific antibodies.Europ. J. Immunol(1993). (In press)."},{"key":"e_1_2_1_5_1","first-page":"175","article-title":"Regulation of T\u2010cell differentiation by CD2 and CD28 accessory molecules","volume":"74","author":"de Jong R.","year":"1991","journal-title":"Immunology"},{"key":"e_1_2_1_6_1","first-page":"660","article-title":"The cell of origin in Hodgkin's disease","volume":"17","author":"Diehl V.","year":"1990","journal-title":"Sem. 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