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Sci Rep. 2017 Oct 17;7(1):13373. doi: 10.1038/s41598-017-13682-9.

Placenta-specific1 (PLAC1) is a potential target for antibody-drug conjugate-based prostate cancer immunotherapy.

Author information

1
Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
2
Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
3
Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran. zarnani@ari.ir.
4
Immunology Research Center, Iran University of Medical Sciences, IUMS, Tehran, Iran. zarnani@ari.ir.
5
Oncopathology Research Center, Iran University of Medical Sciences, IUMS, Tehran, Iran.
6
Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, IUMS, Tehran, Iran.
7
Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
8
Department of Pathology, Hasheminejad Kidney Center, Iran University of Medical Sciences, IUMS, Tehran, Iran.
9
Veterinary department, Islamic Azad University, Abhar branch, Abhar, Iran.
10
Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), Tehran, Iran. dinarvand@tums.ac.ir.
11
Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. dinarvand@tums.ac.ir.

Abstract

Our recent findings strongly support the idea of PLAC1 being as a potential immunotherapeutic target in prostate cancer (PCa). Here, we have generated and evaluated an anti-placenta-specific1 (PLAC1)-based antibody drug conjugate (ADC) for targeted immunotherapy of PCa. Prostate cancer cells express considerable levels of PLAC1. The Anti-PLAC1 clone, 2H12C12, showed high reactivity with recombinant PLAC1 and selectivity recognized PLAC1 in prostate cancer cells but not in LS180 cells, the negative control. PLAC1 binding induced rapid internalization of the antibody within a few minutes which reached to about 50% after 15 min and almost completed within an hour. After SN38 conjugation to antibody, a drug-antibody ratio (DAR) of about 5.5 was achieved without apparent negative effect on antibody affinity to cell surface antigen. The ADC retained intrinsic antibody activity and showed enhanced and selective cytotoxicity with an IC50 of 62 nM which was about 15-fold lower compared to free drug. Anti-PLAC1-ADC induced apoptosis in human primary prostate cancer cells and prostate cell lines. No apparent cytotoxic effect was observed in in vivo animal safety experiments. Our newly developed anti-PLAC1-based ADCs might pave the way for a reliable, efficient, and novel immunotherapeutic modality for patients with PCa.

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