The application of immunotargeting into cancer chemotherapy with carboplatin: in vitro and in vivo studies.
Anti-tumor effects of the following 2 cis-diammin (1, 1-cyclobutandicarboxylato) platin II (carboplatin, Bristol-Myers-Squibb) conjugates were evaluated through both in vitro and in vivo experiments: (1) carboplatin coupled with anti-cytokeratin monoclonal antibody (MAb), TS1 via carboxymethyl dextran (carboplatin-carboxymethyl dextran-TS1), and (2) carboplatin-carboxymethyl dextran-avidin targeted to biotinylated TS1. Using 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide and N-hydroxysuccinimide, carboplatin was conjugated to carboxymethyl dextran, TS1, or avidin, at high molar ratios. The staining positivity of carboplatin-carboxymethyl dextran-TS1 in indirect immunofluorescence was almost identical to that of the original MAb. The average dose of carboplatin given in each treatment was about 60% of a clinical dose. Regarding cytotoxicity, the free drug showed the strongest effect and the best dose-dependency in cell lines: HeLa and ZR-75-1. An in vivo study giving carboplatin-MAb conjugates or free drug to HeLa tumor bearing nude rats proved that the efficacy of carboplatin-carboxymethyl dextran-TS1 in HeLa tumor was not greater than that of the free carboplatin.
Ota
Y
Y
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Chiba, Japan.
Oehr
P
P
Inaba
N
N
Takamizawa
H
H
D000818:Animals; D000911:Antibodies, Monoclonal; D016190:Carboplatin / Q000627:therapeutic use*; D003911:Dextrans; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D051381:Rats
D000911:Antibodies, Monoclonal; D003911:Dextrans; D000922:Immunotoxins; C014392:carboxymethyl dextran; D016190:Carboplatin