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

  • Andri Wardiana Research Centre for Biotechnology, Indonesian Institute of Sciences (LIPI). Jl. Raya Bogor Km 46, 16911, West Java, Indonesia
  • Martina L Jones Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, 4072 QLD, Australia
  • Stephen M Mahler Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, 4072 QLD, Australia;
  • Christopher B Howard Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, 4072 QLD, Australia
Keywords: Amino Acid

Abstract

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.

Author Biographies

Stephen M Mahler, Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, 4072 QLD, Australia;

Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, 4072 QLD, Australia; ARC Training Centre for Biopharmaceutical Innovation, Corner College and Cooper Rds (Bldg 75), The University of Queensland, Brisbane, QLD 4072, Australia

Christopher B Howard, Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, 4072 QLD, Australia

Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, 4072 QLD, Australia ARC Training Centre for Biopharmaceutical Innovation, Corner College and Cooper Rds (Bldg 75), The University of Queensland, Brisbane, QLD 4072, Australia

References

K.F. Brown, H. Rumgay, C. Dunlop, M. Ryan, F. Quartly, A. Cox, A. Deas, L. Ellis-Brookes, A. Gavin, L. Hounsome, D. Huws, N. Ormiston-Smith, J. Shelton, C. White, D.M. Parkin, Br. J. Cancer 118, 8 (2015)
Published
2021-03-15
How to Cite
Wardiana, A., Jones, M. L., Mahler, S. M., & Howard, C. B. (2021). Incorporation of Unnatural Amino Acid into Antibody Fragment for Creating a Stable Antibody Drug Conjugate. Indonesian Journal of Pharmacy, 32(1), 96-105. https://doi.org/10.22146/ijp.1101
Section
Research Article