Abstract
We have produced an adriamycin-conjugated monoclonal antibody, AMI, covalently linked by acid-labilecis-aconitic spacer. The immunoconjugate,cis- aconitic adriamycin (cAA)-AMl, was confirmed to retain the binding activity against human breast cancer cell lines by flow cytometry. The immunoconjugate was shown to be internalized into antigen-positive cancer cells by flow cytometry analysis and high performance liquid chromatography. Antitumor effects of cAA-AMl were assessed on human breast cancer and colon cancer cell lines, with inhibition of3H leucine uptakes to the cells. cAA-AM1 demonstrated a selective cytotoxicity to ZR-75- 1 which was reactive with AMI, whereas it showed no antitumor effect on SW1116 cells which did not react with AMI. Free adriamycin demonstrated a non-selective cytotoxicity against both cell lines. AMI alone and cAA-control IgM did not show any antitumor effect on ZR-75-1. These results suggest that cAA-AMl retains binding activity and specificity against breast cancer cellsin vitro.
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Abbreviations
- ADM:
-
Adriamycin
- cAA:
-
cis-Aconitic-adriamycin
- MAb:
-
Monoclonal antibody
- HPLC:
-
High performance liquid chromatography
- DMEM:
-
Dulbecco’s modified Eagle’s minimal essential medium
- FCS:
-
Fetal calf serum
- HEPES:
-
HydroxyethylpiperazineN’-2-ethansulfonic acid; EDC, N - Ethyl-N’- [(3-dimethyl-amino)propyl] carbodiimide hydrochloride
- MSR:
-
Molar substitution rario
- BSA:
-
Bovine serum albumin
- MFI:
-
Mean fluorescence intensity
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Ikegaki, H., Ohuchi, N., Masuko, T. et al. Characterization andin vitro cytotoxic effect of adriamycin conjugated monoclonal antibody prepared against breast cancer cell line. Breast Cancer 4, 85–92 (1997). https://doi.org/10.1007/BF02967061
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DOI: https://doi.org/10.1007/BF02967061