{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:07:21Z","timestamp":1790935641908,"version":"4.1.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2007,5,1]],"date-time":"2007-05-01T00:00:00Z","timestamp":1177977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The therapeutic mAb rituximab induced the expression of the CCL3 and CCL4 chemokines in the human lymphoma line BJAB following binding to the CD20 Ag. Induction of CCL3\/4 in vitro was specific, was observed in several cell lines and freshly isolated lymphoma samples and also took place at the protein level in vitro and in vivo. To investigate the role of these \u03b2-chemokines in the mechanism of action of rituximab, we synthesized a N-terminally truncated CCL3 molecule CCL3(11\u201370), which had antagonist activity on chemotaxis mediated by either CCL3 or BJAB supernatant. We also set up an established s.c. BJAB tumor model in athymic mice. Rituximab, given weekly after tumors had reached 250 mm2, led to complete disappearance of the lymphoma within 2\u20133 wk. Treatment of mice with cobra venom factor showed that complement was required for rituximab therapeutic activity. Treatment of BJAB tumor bearing mice every 2 days with the CCL3(11\u201370) antagonist, starting 1 wk before rituximab treatment, had no effect on tumor growth by itself, but completely inhibited the therapeutic activity of the Ab. To determine whether CCL3 acts through recruitment\/activation of immune cells, we specifically depleted NK cells, polymorphonuclear cells, and macrophages using mAbs, clodronate treatment, or Rag2\u2212\/\u2212c\u03b3\u2212\/\u2212 mice. The data demonstrated that these different cell populations are involved in BJAB tumor eradication. We propose that rituximab rapidly activates complement and induces \u03b2-chemokines in vivo, which in turn activate the innate immunity network required for efficient eradication of the bulky BJAB tumor.<\/jats:p>","DOI":"10.4049\/jimmunol.178.10.6616","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T22:53:28Z","timestamp":1397861608000},"page":"6616-6623","source":"Crossref","is-referenced-by-count":44,"title":["The CCL3 Family of Chemokines and Innate Immunity Cooperate In Vivo in the Eradication of an Established Lymphoma Xenograft by Rituximab"],"prefix":"10.1093","volume":"178","author":[{"given":"Elena","family":"Cittera","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Gene Therapy \u201cG. Lanzani,\u201d Division of Haematology, Ospedali Riuniti di Bergamo , Bergamo ,","place":["Italy"]},{"name":"Laboratory of Molecular Immunohaematology, Istituto Ricerche Farmacologiche Mario Negri , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Leidi","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Gene Therapy \u201cG. Lanzani,\u201d Division of Haematology, Ospedali Riuniti di Bergamo , Bergamo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Buracchi","sequence":"additional","affiliation":[{"name":"Research Laboratories of Immunology and Inflammation, Istituto Clinico Humanitas, Istituti di Ricovero e Cura a Carattere Scientifico , Rozzano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Pasqualini","sequence":"additional","affiliation":[{"name":"Research Laboratories of Immunology and Inflammation, Istituto Clinico Humanitas, Istituti di Ricovero e Cura a Carattere Scientifico , Rozzano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvano","family":"Sozzani","sequence":"additional","affiliation":[{"name":"Section of General Pathology, University of Brescia , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annunciata","family":"Vecchi","sequence":"additional","affiliation":[{"name":"Research Laboratories of Immunology and Inflammation, Istituto Clinico Humanitas, Istituti di Ricovero e Cura a Carattere Scientifico , Rozzano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Douglas","family":"Waterfield","sequence":"additional","affiliation":[{"name":"University of British Columbia , Vancouver, British Columbia ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martino","family":"Introna","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Gene Therapy \u201cG. 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