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Selective toxicity of neocarzinostatin-monoclonal antibody conjugates to the antigen-bearing human melanoma cell line in vitro

Summary

Monoclonal antibodies (IgG1) against high molecular weight antigen A-1-43 on human melanoma cell line A-375 were successfully linked to the anti-tumour protein neocarzinostatin (NCS) using the heterobifunctional reagent N-succinimidyl 3-(2-pyridyldithio)-propionate (SPDP). The conjugate retained both the reactivity of the antibody and the toxicity of the drug. The antigen-bearing cell line A-375, antigen-lacking cell line MeWo and normal skin fibroblasts were exposed to NCS-monoclonal antibody conjugates. As negative control, cells were also treated with free NCS and NCS coupled to normal mouse IgG1 antibodies. Inhibition of 3H-thymidine uptake after treatment was used to measure the biological activity of the cytotoxic drug complex or substance, respectively.

Comparing the inhibition dose for 50% uptake (ID50) it was found that the monoclonal antibody-drug complex is about 100 times more toxic for the antigen-bearing cell line than free NCS or normal mouse IgG1-NCS. This high toxicity is due to a local increase of drug concentration on these cells. With the two cell lines lacking the appropriate antigen no significant differences in the ID50 values were observed. A selectivity factor of 40–50 was obtained by comparing the cytotoxic effect of the monoclonal antibody-NCS conjugate upon the antigen-bearing as opposed to the antigen-lacking cell type. These data demonstrate, that the toxicity of NCS can be directed by monoclonal antibodies to human tumour cells carrying the corresponding surface antigen.

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Correspondence to W. Köhnlein.

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Lüders, G., Köhnlein, W., Sorg, C. et al. Selective toxicity of neocarzinostatin-monoclonal antibody conjugates to the antigen-bearing human melanoma cell line in vitro. Cancer Immunol Immunother 20, 85–90 (1985). https://doi.org/10.1007/BF00199779

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Keywords

  • Normal Mouse
  • Skin Fibroblast
  • Selectivity Factor
  • Antibody Conjugate
  • Human Melanoma Cell Line