{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T15:33:36Z","timestamp":1760888016777},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,7,17]],"date-time":"2006-07-17T00:00:00Z","timestamp":1153094400000},"content-version":"vor","delay-in-days":4535,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[1994,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The successful clinical experience with antibody LL2 (an IgG<jats:sub>2a<\/jats:sub>, anti\u2010B\u2010cell lymphoma antibody) in radipimmunodetection and radioimmunotherapy suggests that this antibody may have potential as a carrier of cytotoxic agents. The internalization, cellular trafficking, and catabolism of this antibody in target human Burkitt lymphoma cells (Raji) were investigated. Internalization of intact antibody as well as of the F(ab')<jats:sub>2<\/jats:sub> and Fab' fragments was detected by an FITC\u2010labeled anti\u2010mouse second antibody probe, and evaluated by fluorescence microscopy. Internalization of intact IgG (or the fragments) was observed as early as 5 min after incubation at 37\u00b0C. Initially, the internalized antibodies were present as micro\u2010particles inside the cell membrane, and were translocated to the lysosomal compartment within 2 hr. The anatomic location of the internalized antibody, before translocation to the lysosomal compartment, was deduced by comparing the fluorescence images obtained with the antibody to those obtained with fluorescent probes with known cellular distribution in a co\u2010internalization study. A Golgi\u2010like compartment was found to be involved in the translocation of the antibody. Cellular catabolism of the bound antibody was studied by using <jats:sup>125<\/jats:sup>I\u2010labeled antibody on the target cells. At 21 h, 40% of the radioactivity was released into the supernatant as degraded fragments. The observation suggested that the antibody was degraded mainly in the lysosomes, since the degradation was significantly inhibited in the presence of lysosomal inhibitors such as ammonium chloride or leupeptin. Subcellular fractionation of Raji cells after the binding of <jats:sup>125<\/jats:sup>I\u2010lbeled LL2 indicated that the antibody was translocated to lysosomes as evidenced by SDS\u2010PAGE. The rate of internalization (K) of LL2, and the re\u2010expression of the antigen were determined. The rapid Internalization of LL2 and the reexpression of the antigen suggest that this antibody may have potential as a therapeutic immunoconjugate, since it could deliver a higher accumulation of cytotoxic agents into lymphoma cells.<\/jats:p>","DOI":"10.1002\/ijc.2910560413","type":"journal-article","created":{"date-parts":[[2007,2,20]],"date-time":"2007-02-20T00:14:06Z","timestamp":1171930446000},"page":"538-545","source":"Crossref","is-referenced-by-count":62,"title":["Internalization and intracellular processing of an anti B\u2010cell lymphoma monoclonal antibody, ll2"],"prefix":"10.1002","volume":"56","author":[{"given":"Lisa B.","family":"Shih","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen H.\u2010Z.","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Xuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Goldenberg","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":"10.1007\/BF01741596"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/81.19.1455"},{"key":"e_1_2_1_4_1","first-page":"2907","article-title":"Intracellular catabolism of radiolabeled anti\u2010\u03bc antibodies by malignant B\u2010cells","volume":"52","author":"Geissler F.","year":"1992","journal-title":"Cancer Res."},{"key":"e_1_2_1_5_1","first-page":"2610","article-title":"Evaluation of ricin A chain\u2010containing immunotoxins directed against CD19 and CD22 antigens on normal and malignant human B\u2010cells as potential reagents for in vivo therapy","volume":"48","author":"Ghetie M.\u2010A.","year":"1988","journal-title":"Cancer Res."},{"key":"e_1_2_1_6_1","first-page":"5876","article-title":"Antitumor activity of Fab' and IgG\u2010anti\u2010CD22 immunotoxins in disseminated human B lymphoma grown in mice with severe combined immunodeficiency disease: effect on tumor cells in extranodal sites","volume":"51","author":"Ghetie M.\u2010A.","year":"1991","journal-title":"Cancer Res."},{"key":"e_1_2_1_7_1","first-page":"6243","article-title":"Studies on the mechanism of action of abrin\u20109.2.27 immunotoxin in human melanoma cell lines","volume":"47","author":"Godal A.","year":"1987","journal-title":"Cancer Res."},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0001-2998(89)80025-X"},{"key":"e_1_2_1_9_1","first-page":"413","volume-title":"Immunity to cancer","author":"Goldenberg D. 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