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

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 tradition...

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Autores principales: Kang, Xiuhua, Zhou, Li, Jian, Ya-mei, Lan, Shao-an, Xu, Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855927/
https://www.ncbi.nlm.nih.gov/pubmed/29515096
http://dx.doi.org/10.12659/MSM.908971
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author Kang, Xiuhua
Zhou, Li
Jian, Ya-mei
Lan, Shao-an
Xu, Fei
author_facet Kang, Xiuhua
Zhou, Li
Jian, Ya-mei
Lan, Shao-an
Xu, Fei
author_sort Kang, Xiuhua
collection PubMed
description 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/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.
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spelling pubmed-58559272018-03-19 Effectiveness of Antibody-Drug Conjugate (ADC): Results of In Vitro and In Vivo Studies Kang, Xiuhua Zhou, Li Jian, Ya-mei Lan, Shao-an Xu, Fei Med Sci Monit Lab/In Vitro Research 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/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. International Scientific Literature, Inc. 2018-03-08 /pmc/articles/PMC5855927/ /pubmed/29515096 http://dx.doi.org/10.12659/MSM.908971 Text en © Med Sci Monit, 2018 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Lab/In Vitro Research
Kang, Xiuhua
Zhou, Li
Jian, Ya-mei
Lan, Shao-an
Xu, Fei
Effectiveness of Antibody-Drug Conjugate (ADC): Results of In Vitro and In Vivo Studies
title Effectiveness of Antibody-Drug Conjugate (ADC): Results of In Vitro and In Vivo Studies
title_full Effectiveness of Antibody-Drug Conjugate (ADC): Results of In Vitro and In Vivo Studies
title_fullStr Effectiveness of Antibody-Drug Conjugate (ADC): Results of In Vitro and In Vivo Studies
title_full_unstemmed Effectiveness of Antibody-Drug Conjugate (ADC): Results of In Vitro and In Vivo Studies
title_short Effectiveness of Antibody-Drug Conjugate (ADC): Results of In Vitro and In Vivo Studies
title_sort effectiveness of antibody-drug conjugate (adc): results of in vitro and in vivo studies
topic Lab/In Vitro Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855927/
https://www.ncbi.nlm.nih.gov/pubmed/29515096
http://dx.doi.org/10.12659/MSM.908971
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