Synthesis and antitumor activity of the immunoconjugate BR96-Dox
BR96-Dox is an immunoconjugate (IC) in which doxorubicin (8 equivalents) is linked via an acid-labile hydrazone to the chimeric MAb BR96. It binds to a modified Le y Ag on tumor cells, which then internalize it via endocytosis into lysosomes. There, the acidic milieu hydrolyzes the hydrazone link, r...
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| Published in: | Journal of controlled release Vol. 39; no. 2; pp. 251 - 259 |
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| Language: | English |
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Elsevier B.V
01-05-1996
Elsevier |
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| Abstract | BR96-Dox is an immunoconjugate (IC) in which doxorubicin (8 equivalents) is linked via an acid-labile hydrazone to the chimeric MAb BR96. It binds to a modified Le
y Ag on tumor cells, which then internalize it via endocytosis into lysosomes. There, the acidic milieu hydrolyzes the hydrazone link, releasing free Dox. In vivo, it is more active and less toxic than untargeted Dox, producing complete remissions and many cures of subcutaneous human breast, lung and colon tumors, as well as disseminated lung tumors. In vivo, only BR96
+ and not BR96
− tumors respond, and ICs with nonbinding Abs are inactive. |
|---|---|
| AbstractList | BR96-Dox is an immunoconjugate (IC) in which doxorubicin (8 equivalents) is linked via an acid-labile hydrazone to the chimeric MAb BR96. It binds to a modified Le
y Ag on tumor cells, which then internalize it via endocytosis into lysosomes. There, the acidic milieu hydrolyzes the hydrazone link, releasing free Dox. In vivo, it is more active and less toxic than untargeted Dox, producing complete remissions and many cures of subcutaneous human breast, lung and colon tumors, as well as disseminated lung tumors. In vivo, only BR96
+ and not BR96
− tumors respond, and ICs with nonbinding Abs are inactive. |
| Author | Hofstead, S.J. Braslawsky, G.R. Trail, P.A. Hellström, K.E. Firestone, R.A. Lasch, S.J. King, H.D. Henderson, A.J. Kaneko, T. Willner, D. Hellström, I. Greenfield, R.S. Casazza, A.M. |
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| Cites_doi | 10.1021/bc00009a001 10.1126/science.8327892 10.1002/jcb.240560102 10.1002/ijc.2910470121 10.1002/ijc.2910520118 10.1007/BF01741596 10.1021/bc00024a015 |
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| Keywords | PBS Antibody-mediated targeting Ab MR Acid-labile hydrazone Ag Fab Lysosome ip Dox Doxorubicin iv MAb SPDP MST CR sc Endocytosis Le y IC Hydrazone MTD Fc Antitumor targeting Antineoplastic agent Biological fixation Anthracyclins Monoclonal antibody Immunoconjugate Conjugated compound Chemical synthesis Biological activity Tumor cell |
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| Snippet | BR96-Dox is an immunoconjugate (IC) in which doxorubicin (8 equivalents) is linked via an acid-labile hydrazone to the chimeric MAb BR96. It binds to a... |
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| SubjectTerms | Acid-labile hydrazone Antibody-mediated targeting Antineoplastic agents Antitumor targeting Biological and medical sciences Doxorubicin Endocytosis General aspects Hydrazone Lysosome Medical sciences Pharmacology. Drug treatments |
| Title | Synthesis and antitumor activity of the immunoconjugate BR96-Dox |
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