Development of antibody drug conjugates for cancer therapy

Antibody Drug Conjugates (ADC), are biopharmaceutical drugs that are used in cancer treatment. It comprises of an antibody portion that targets the cancer cells and a conjugated cytotoxic drug to kill them. This project aims to develop a novel approach towards ADC production by utilizing Butelase1 (...

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Main Author: Alif Sufiyan Ali
Other Authors: Liu Chuan Fa
Format: Final Year Project
Language:English
Published: 2018
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Online Access:http://hdl.handle.net/10356/74400
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-744002023-02-28T18:07:21Z Development of antibody drug conjugates for cancer therapy Alif Sufiyan Ali Liu Chuan Fa School of Biological Sciences DRNTU::Science Antibody Drug Conjugates (ADC), are biopharmaceutical drugs that are used in cancer treatment. It comprises of an antibody portion that targets the cancer cells and a conjugated cytotoxic drug to kill them. This project aims to develop a novel approach towards ADC production by utilizing Butelase1 (a peptide ligase) to specifically modify Herceptin enzymatically. Traditional methods of manufacturing ADC involves chemical modifications which introduces heterogeneous products of varying antibody-to-drug ratio, that may be toxic. In this FYP, attempts to express His-tag-TEV-Her2-GS-NHV (fusion protein of Herceptin heavy chain with NHV recognition motif and his-tag) was made via molecular cloning, lentiviral packaging, mammalian cell culture and protein purification. Results showed that the molecular cloning to produce recombinant plasmid carrying the His-tag-TEV-Her2-GS-NHV gene was successful. However, the expression of His-tag-TEV-Her2-GS-NHV protein was inconclusive as it could not be detected via western blotting. Moreover, Butelase1-mediated modifications experiments conducted were not successful indicating that there could have been complications with regards to purification or expression of His-tag-TEV-Her2-GS-NHV protein. In spite of that, this FYP serves as a positive step forward to spearhead efforts in developing an exquisite approach for homogeneous ADC manufacturing. Bachelor of Science in Biological Sciences 2018-05-17T05:13:24Z 2018-05-17T05:13:24Z 2018 Final Year Project (FYP) http://hdl.handle.net/10356/74400 en Nanyang Technological University 40 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science
spellingShingle DRNTU::Science
Alif Sufiyan Ali
Development of antibody drug conjugates for cancer therapy
description Antibody Drug Conjugates (ADC), are biopharmaceutical drugs that are used in cancer treatment. It comprises of an antibody portion that targets the cancer cells and a conjugated cytotoxic drug to kill them. This project aims to develop a novel approach towards ADC production by utilizing Butelase1 (a peptide ligase) to specifically modify Herceptin enzymatically. Traditional methods of manufacturing ADC involves chemical modifications which introduces heterogeneous products of varying antibody-to-drug ratio, that may be toxic. In this FYP, attempts to express His-tag-TEV-Her2-GS-NHV (fusion protein of Herceptin heavy chain with NHV recognition motif and his-tag) was made via molecular cloning, lentiviral packaging, mammalian cell culture and protein purification. Results showed that the molecular cloning to produce recombinant plasmid carrying the His-tag-TEV-Her2-GS-NHV gene was successful. However, the expression of His-tag-TEV-Her2-GS-NHV protein was inconclusive as it could not be detected via western blotting. Moreover, Butelase1-mediated modifications experiments conducted were not successful indicating that there could have been complications with regards to purification or expression of His-tag-TEV-Her2-GS-NHV protein. In spite of that, this FYP serves as a positive step forward to spearhead efforts in developing an exquisite approach for homogeneous ADC manufacturing.
author2 Liu Chuan Fa
author_facet Liu Chuan Fa
Alif Sufiyan Ali
format Final Year Project
author Alif Sufiyan Ali
author_sort Alif Sufiyan Ali
title Development of antibody drug conjugates for cancer therapy
title_short Development of antibody drug conjugates for cancer therapy
title_full Development of antibody drug conjugates for cancer therapy
title_fullStr Development of antibody drug conjugates for cancer therapy
title_full_unstemmed Development of antibody drug conjugates for cancer therapy
title_sort development of antibody drug conjugates for cancer therapy
publishDate 2018
url http://hdl.handle.net/10356/74400
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