%0 Journal Article
%T PDL-1 Antibody Drug Conjugate for Selective Chemo-Guided Immune Modulation of Cancer
%A Alex Petrovici
%A Arun K. Iyer
%A Hashem O. Alsaab
%A Ketki Bhise
%A Samaresh Sau
%J Archive of "Cancers".
%D 2019
%R 10.3390/cancers11020232
%X 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-¦Ã 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
%K antibody drug conjugate (ADC)
%K PD-L1
%K tumor spheroid disruption
%K immune modulation
%K doxorubicin
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406713/