Effectiveness of Antibody-Drug Conjugate (ADC): Results of In Vitro and In Vivo Studies

• Published in: Medical science monitor 2018-03, Vol.24, p.1408-1416
• Main Authors: Kang, Xiuhua, Zhou, Li, Jian, Ya-Mei, Lan, Shao-An, Xu, Fei
• Format: Article
• Language: English
• Subjects: A549 Cells; Animals; Antibodies - pharmacology; Antibodies - therapeutic use; Apoptosis - drug effects; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Cell Cycle - drug effects; Cell Proliferation - drug effects; Cetuximab - administration & dosage; Cetuximab - pharmacology; Cetuximab - therapeutic use; Cisplatin - administration & dosage; Cisplatin - pharmacology; Cisplatin - therapeutic use; Humans; Immunoconjugates - pharmacology; Immunoconjugates - therapeutic use; Lab/In Vitro Research; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Mice; Tumor Burden - drug effects; Xenograft Model Antitumor Assays
• ISSN: 1643-3750; 1234-1010; 1643-3750
• DOI: 10.12659/MSM.908971

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.