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- Title
Incorporation of Unnatural Amino Acid into Antibody Fragment for Creating a Stable Antibody-Drug Conjugate.
- Authors
Wardiana, Andri; Jones, Martina L.; Mahler, Stephen M.; Howard, Christopher B.
- Abstract
Traditional chemotherapy drugs have been used as a standard treatment for cancers. However, the drugs have resulted in a modest survival benefit and damaged non-cancerous cells. Thus, novel strategies that can improve selectivity and specificity in chemotherapy are urgently needed. An antibody-drug conjugate (ADC), which combines a monoclonal antibody and a cytotoxic drug, is a potential for targeted therapy. However, heterogeneous mixtures have been observed using the current ADC methods. Here, we developed a strategy for generating a stable ADC utilizing a modified singlechain antibody fragment (scFv) containing azide group for click chemistry reaction with alkyne containing the cytotoxic drug. This research focused on targeting prostate cancer as a model disease targeting prostate-specific membrane antigen (PSMA) receptor which is overexpressed in all stages of prostate cancer. The unnatural amino acid, para-azido phenylalanine (pAzF), has been successfully incorporated into anti-PSMA J591 scFv and specifically bound and internalized into PSMA positive cancer cells. This mutant scFv was also successfully conjugated to 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 treatments.
- Subjects
ANTIBODY-drug conjugates; AMINO acids; CHEMICAL reactions; FUNCTIONAL groups; ANTINEOPLASTIC agents
- Publication
Indonesian Journal of Pharmacy / Majalah Farmasi Indonesia, 2021, Vol 32, Issue 1, p96
- ISSN
0126-1037
- Publication type
Article