caa a22 4500 469073691 CHVBK 20180323132929.0 cr unu---uuuuu 170328e19920501xx s 000 0 eng 10.1007/BF01756186 doi (NATIONALLICENCE)springer-10.1007/BF01756186 Immunotargeting of daunomycin to localized and metastatic human colon adenocarcinoma in athymic mice [Elektronische Daten] [Esther Hurwitz, Ruth Adler, Daniel Shouval, Hiroshi Takahashi, Jack Wands, Michael Sela] Summary: A monoclonal antibody (designated SF25), which recognizes a protein antigen expressed on a large number of human colon carcinomas, was used for drug targeting. Daunomycin-antibody conjugates were prepared by two previously described procedures. In one, the drug was bound to the antibody through a spacer of small molecular mass (cis-aconitic acid), while in the other a dextran bridge served as the link between drug and antibody. High substitution rates of drug to antibody were obtained using the latter binding procedure. Both conjugates were tested in vitro against two human colon carcinoma cell lines, LS180 and KM-12. The efficacy of a daunomycin-dextran-SF25 antibody conjugate was tested against colon carcinoma LS180 tumors transplanted at different sites into athymic mice. The specific conjugate was significantly more inhibitory to a subcutaneous tumor growth than its components or their mixture. SF25 antibody alone showed antitumoral effects against all three forms of transplanted tumor tested, namely, local, metastatic or intrahepatic, whereas daunomycin, on its own, was effective only against the subcutaneous tumor. Binding of daunomycin to dextran partially improved its inhibitory activity against the metastatic tumor. The conjugate, daunomycin-dextran-SF25 antibody reduced the number of metastatic foci, increased the survival rate and delayed death. Yet against lymph node metastases it was not significantly better than a mixture of both constituents. However, results obtained with an intrahepatic tumor, a model that mimics the natural progression of the disease, resembled those described with the subcutaneous tumor. Daunomycin-dextran-SF25 antibody was significantly more effective than all components separately and than a mixture of drug and antibody, provided a highly drug-substituted conjugate was used. Springer-Verlag, 1992 Drug immunotargeting nationallicence Metastases nationallicence Colon carcinoma nationallicence Monoclonal antibody nationallicence Hurwitz Esther Department of Chemical Immunology, The Weizmann Institute of Science, 76100, Rehovot, Israel aut Adler Ruth Liver Unit, Department of Medicine, Hadassah University Hospital, 91120, Jerusalem, Israel aut Shouval Daniel Liver Unit, Department of Medicine, Hadassah University Hospital, 91120, Jerusalem, Israel aut Takahashi Hiroshi Molecular Hepatology Center, Massachusetts General Hospital, 02114, Boston, MA, USA aut Wands Jack Molecular Hepatology Center, Massachusetts General Hospital, 02114, Boston, MA, USA aut Sela Michael Department of Chemical Immunology, The Weizmann Institute of Science, 76100, Rehovot, Israel aut Cancer Immunology, Immunotherapy Springer-Verlag 35/3(1992-05-01), 186-192 0340-7004 35:3<186 1992 35 262 https://doi.org/10.1007/BF01756186 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01756186 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hurwitz Esther Department of Chemical Immunology, The Weizmann Institute of Science, 76100, Rehovot, Israel aut NATIONALLICENCE 700 1- Adler Ruth Liver Unit, Department of Medicine, Hadassah University Hospital, 91120, Jerusalem, Israel aut NATIONALLICENCE 700 1- Shouval Daniel Liver Unit, Department of Medicine, Hadassah University Hospital, 91120, Jerusalem, Israel aut NATIONALLICENCE 700 1- Takahashi Hiroshi Molecular Hepatology Center, Massachusetts General Hospital, 02114, Boston, MA, USA aut NATIONALLICENCE 700 1- Wands Jack Molecular Hepatology Center, Massachusetts General Hospital, 02114, Boston, MA, USA aut NATIONALLICENCE 700 1- Sela Michael Department of Chemical Immunology, The Weizmann Institute of Science, 76100, Rehovot, Israel aut NATIONALLICENCE 773 0- Cancer Immunology, Immunotherapy Springer-Verlag 35/3(1992-05-01), 186-192 0340-7004 35:3<186 1992 35 262 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer