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

Samaresh SauAlex PetroviciHashem O AlsaabKetki BhiseArun K Iyer
Published in: Cancers (2019)
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.
Keyphrases
  • cancer therapy
  • drug delivery
  • high resolution
  • oxidative stress
  • photodynamic therapy
  • squamous cell carcinoma
  • poor prognosis
  • emergency department
  • cell death
  • young adults