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Preparation of Anti-EGFR Monoclonal Antibody Immunoconjugate (EQ75-ADR) and It's Inhibitory Effect on Human Epidermoid Carcinoma
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Abstract:
To prepare an immunoconjugate of anti-EGFR monoclonal antibody (EQ75) and adriamycin (ADR) and to investigute it's inhibitory effect on human epidermoid carcinoma (A431) in vitro and in vivo and it's side effect on C57BL/6J mice. Methods: The immunoconjugate (EQ75-ADR) was prepared with animproved glutaraldehyde conjugate method and the cytotoxicity effects of EQ75-ADR on A431 cells and Wish cells were measured by MTT assay. A431 tumor-bearing nude mice and C57BL/6J experimental model were established and were used for testing the inhibitory effects of EQ75-ADR. The side effect of EQ75-ADR was compared with ADR. Results: The EQ75-ADR showed specific cytotoxicity on A431cells, the cytotoxicity of EQ75-ADR was 50-fold, 14-fold and 10-fold more efficient than that of EQ75, ADR and mixture of EQ75 and ADR (EQ75+ADR) respectively. The effect of EQ75-ADR on with cells was 10-fold less efficient than that of ADR and EQ75+ADR. As compared with the cytoxicity effect of EQ75-ADR on Wish cells with A431 cells, it showed 300-fold less efficient. Similar cytotoxicity results were shown in 2 h treatment experimental group. The EQ75-ADR exhibited significant anti-tumor activity on tumor-bearing nude mice, and the inhibition rate is 92.2% (P<0.01). As compared with ADR, it's side effect was much lower. Conclusion: The EQ75-ADR exhibited targeted delivery and striking anti-tumor activity in vitro and in vivo and this approach appears a promising future for clinic purpose.
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