Abstract

BACKGROUND: Human lung cancer is still the leading cause of cancer-related mortality around the world, although a variety of new therapies have been used in the treatment of this disease. Antibody-drug conjugate (ADC) has revolutionized the field of cancer therapy in recent decades. Unlike traditional chemotherapy that damages the healthy cells, ADC first utilizes monoclonal antibodies to bind tumor-specific antigen targets and then deliver a highly potent cytotoxic agent to kill tumor cells. Thus, ADC can benefit cancer patients because this drug has less severe adverse effects.

MATERIAL AND METHODS: One type of ADC for non-small cell lung cancer (NSCLC) was designed in this study: Erbitux-vc-PAB-MMAE. It is a mouse/human chimeric monoclonal antibody, Erbitux, conjugating to the tubulin inhibitor auristatin. The efficacy of ADC was investigated through in vitro and in vivo studies.

RESULTS: Our in vitro study demonstrated that Erbitux-vc-PAB-MMAE could effectively inhibit proliferation of human lung cancer A549 cells, and arrested cell cycle at G2/M phase. In a mouse xenograft model, the results indicated that Erbitux-vc-PAB-MMAE could be exactly delivered to tumor tissues, and effectively inhibited tumor growth via promoting apoptosis of cancer cells.

CONCLUSIONS: The antibody portion of an ADC drug (Erbitux) was used as a vector to bring the effector molecule (tubulin inhibitor MMAE) to the targeted tumor tissue. This antibody-drug conjugate can exert a strong anti-tumor effect.

Keywords: Antibodies, Monoclonal, Immunotoxins