Incorporation of Unnatural Amino Acid into Antibody Fragment for Creating a Stable Antibody Drug Conjugate

The traditional chemotherapy drug has been used as a standard cancer treatment, however it has resulted a modest survival benefit and damaged non-cancerous cells. Thus, the novel strategies which can improve selectivity and specificity in chemotherapy are urgently needed. Antibody drug conjugate (AD...

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Autores principales:	Andri Wardiana, Martina L Jones, Stephen M Mahler, Christopher B Howard
Formato:	article
Lenguaje:	EN
Publicado:	Universitas Gadjah Mada 2021
Materias:	amino acid Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/02e0cdb3dc284c18b07c1cbd8758cd07
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spelling	oai:doaj.org-article:02e0cdb3dc284c18b07c1cbd8758cd072021-11-15T06:08:47ZIncorporation of Unnatural Amino Acid into Antibody Fragment for Creating a Stable Antibody Drug Conjugate2338-94272338-948610.22146/ijp.1101https://doaj.org/article/02e0cdb3dc284c18b07c1cbd8758cd072021-03-01T00:00:00Zhttps://jurnal.ugm.ac.id/v3/IJP/article/view/1101https://doaj.org/toc/2338-9427https://doaj.org/toc/2338-9486The traditional chemotherapy drug has been used as a standard cancer treatment, however it has resulted a modest survival benefit and damaged non-cancerous cells. Thus, the novel strategies which can improve selectivity and specificity in chemotherapy are urgently needed. Antibody drug conjugate (ADC) combines monoclonal antibody and cytotoxic drug is a potential regimen as targeted therapy. However, the heterogeneous mixtures has been observed using the current ADC methods. Here, we develop the strategy for generation a stable ADC utilising modified single chain antibody fragment (scFv) containing azide group for click chemistry reaction with alkyne containing cytotoxic drug. This research focused on targeting prostate cancer as a model disease utilising targeting prostate specific membrane antigen (PSMA) receptor which is overexpressed in all prostate cancer stages. The unnatural amino acid para-azido phenyl alanine (pAzF) has been successfully incorporated into anti-PSMA J591 scFv and specifically bound and internalised into PSMA positive cancer cells. This mutant scFv were also successfully conjugated into a linker containing cyclo-alkyne, DBCO-PEG4-DBCO as a model for creating ADC through copper-free click chemistry reaction. This bioconjugation method is promising as a versatile strategy for generating a stable ADC to improve therapeutic efficacy in cancer treatment.Andri WardianaMartina L JonesStephen M MahlerChristopher B HowardUniversitas Gadjah Madaarticleamino acidPharmacy and materia medicaRS1-441ENIndonesian Journal of Pharmacy, Pp 96-105 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	amino acid Pharmacy and materia medica RS1-441
spellingShingle	amino acid Pharmacy and materia medica RS1-441 Andri Wardiana Martina L Jones Stephen M Mahler Christopher B Howard Incorporation of Unnatural Amino Acid into Antibody Fragment for Creating a Stable Antibody Drug Conjugate
description	The traditional chemotherapy drug has been used as a standard cancer treatment, however it has resulted a modest survival benefit and damaged non-cancerous cells. Thus, the novel strategies which can improve selectivity and specificity in chemotherapy are urgently needed. Antibody drug conjugate (ADC) combines monoclonal antibody and cytotoxic drug is a potential regimen as targeted therapy. However, the heterogeneous mixtures has been observed using the current ADC methods. Here, we develop the strategy for generation a stable ADC utilising modified single chain antibody fragment (scFv) containing azide group for click chemistry reaction with alkyne containing cytotoxic drug. This research focused on targeting prostate cancer as a model disease utilising targeting prostate specific membrane antigen (PSMA) receptor which is overexpressed in all prostate cancer stages. The unnatural amino acid para-azido phenyl alanine (pAzF) has been successfully incorporated into anti-PSMA J591 scFv and specifically bound and internalised into PSMA positive cancer cells. This mutant scFv were also successfully conjugated into a linker containing cyclo-alkyne, DBCO-PEG4-DBCO as a model for creating ADC through copper-free click chemistry reaction. This bioconjugation method is promising as a versatile strategy for generating a stable ADC to improve therapeutic efficacy in cancer treatment.
format	article
author	Andri Wardiana Martina L Jones Stephen M Mahler Christopher B Howard
author_facet	Andri Wardiana Martina L Jones Stephen M Mahler Christopher B Howard
author_sort	Andri Wardiana
title	Incorporation of Unnatural Amino Acid into Antibody Fragment for Creating a Stable Antibody Drug Conjugate
title_short	Incorporation of Unnatural Amino Acid into Antibody Fragment for Creating a Stable Antibody Drug Conjugate
title_full	Incorporation of Unnatural Amino Acid into Antibody Fragment for Creating a Stable Antibody Drug Conjugate
title_fullStr	Incorporation of Unnatural Amino Acid into Antibody Fragment for Creating a Stable Antibody Drug Conjugate
title_full_unstemmed	Incorporation of Unnatural Amino Acid into Antibody Fragment for Creating a Stable Antibody Drug Conjugate
title_sort	incorporation of unnatural amino acid into antibody fragment for creating a stable antibody drug conjugate
publisher	Universitas Gadjah Mada
publishDate	2021
url	https://doaj.org/article/02e0cdb3dc284c18b07c1cbd8758cd07
work_keys_str_mv	AT andriwardiana incorporationofunnaturalaminoacidintoantibodyfragmentforcreatingastableantibodydrugconjugate AT martinaljones incorporationofunnaturalaminoacidintoantibodyfragmentforcreatingastableantibodydrugconjugate AT stephenmmahler incorporationofunnaturalaminoacidintoantibodyfragmentforcreatingastableantibodydrugconjugate AT christopherbhoward incorporationofunnaturalaminoacidintoantibodyfragmentforcreatingastableantibodydrugconjugate
_version_	1718428533940813824

Incorporation of Unnatural Amino Acid into Antibody Fragment for Creating a Stable Antibody Drug Conjugate

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