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Cancers 2019, 11(2), 232; https://doi.org/10.3390/cancers11020232

PDL-1 Antibody Drug Conjugate for Selective Chemo-Guided Immune Modulation of Cancer

1
Department of Pharmaceutical Sciences, Wayne State University Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Detroit, MI 48201, USA
2
Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taif University, Taif 26571, Saudi Arabia
3
Molecular Imaging Program, Barbara Ann Karmanos Cancer Institute. Wayne State University School of Medicine, 4100 John R St, Detroit, MI 48201, USA
*
Authors to whom correspondence should be addressed.
Received: 23 January 2019 / Revised: 8 February 2019 / Accepted: 14 February 2019 / Published: 16 February 2019
(This article belongs to the Special Issue Cancer Nanomedicine)
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Abstract

Targeting immune checkpoint molecules such as programmed death ligand-1 (PDL1) is an emerging strategy for anti-cancer therapy. However, transient expression of PDL1 and difficulty in tumor stroma penetration has limited the utility of anti-PDL1 therapy. To overcome these limitations, we report a new conjugate between the clinically approved PDL1 antibody (PDL1 AB) and drug Doxorubicin (Dox), named PDL1-Dox. We conjugated PDL1-Dox through a hydrazone linker containing a polyethylene glycol (PEG) spacer, which allows it to dissociate in a tumor environment and improves solubility. The purpose of using Dox is to disrupt the tumor extracellular environment so that PDL-1 antibody can penetrate the tumor core. PDL1-Dox demonstrates significant cell killing, disruption of tumor spheroid and induction of apoptosis in a breast cancer cell line. Significant release of IFN-γ suggests PDL1-Dox can upmodulate T cell activation. Optical imaging of dye conjugate supports the selective tumor targeting ability and core penetration of the construct. View Full-Text
Keywords: antibody drug conjugate (ADC); PD-L1; tumor spheroid disruption; immune modulation; doxorubicin antibody drug conjugate (ADC); PD-L1; tumor spheroid disruption; immune modulation; doxorubicin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Sau, S.; Petrovici, A.; Alsaab, H.O.; Bhise, K.; Iyer, A.K. PDL-1 Antibody Drug Conjugate for Selective Chemo-Guided Immune Modulation of Cancer. Cancers 2019, 11, 232.

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