Z-domain protein nano-bio interfaced MRI visible anti-program death ligand-1 nanoconjugates for enhanced local immune checkpoint inhibitor immunotherapy

Bongseo Choi, Hyunjun Choi, Heegon Kim, Ashley Choi, Soon Woo Kwon, Samdeep K. Mouli, Robert J. Lewandowski, Dong Hyun Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Monoclonal antibody (mAb) based immune checkpoint inhibitors (ICIs) have emerged as an effective and promising therapeutic agent for cancer immunotherapy. In the setting of tumor immune-suppression, an effective delivery of mAbs ICI might be essential to overcome tumor resistance, immune tolerance, and immune-related adverse effects (irAEs). Herein we report engineered MRI visible anti-programmed cell death ligand-1 mAb (aPD-L1) nanoconjugates using nano-bio interface Z-domain (Z) protein adaptors for the local ICI immunotherapy. Z protein adaptors, which are binding with Fc region of IgG mAb, were modified to be attached on the surface of MRI visible ferumoxytol (Fer). Z-protein adaptors on the surface of Fer allowed an oriented conjugation of aPD-L1 exposing active Fab binding sites outward for effective blockage of immune checkpoints. Enhanced affinity and avidity of engineered Z mediated aPD-L1 nanoconjugates (aPD-L1-Z-Fer) to block the PD-1/PD-L1 axis were demonstrated in vitro and in vivo. Transcatheter-directed hepatic intra-arterial (IA) infusion of aPD-L1-Z-Fer showed superior in vivo hepatocellular carcinoma (HCC) tumor suppression, immune conversion, and minimized irAEs compared to the experimental groups treated with systemic aPD-L1, local aPD-L1, or chemically conjugated aPD-L1@Fer. Nano-bio interface Z protein adaptors mediated conjugation of functional nanoparticles and mAbs ICI will provide a new avenue to expand local ICI immunotherapy.

Original languageEnglish (US)
Article number101552
JournalNano Today
Volume45
DOIs
StatePublished - Aug 2022

Keywords

  • Hepatocellular carcinoma
  • Image-guided cancer therapy
  • Immune checkpoint inhibitor
  • Transcatheter local immunotherapy
  • Z-domain

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • General Materials Science
  • Pharmaceutical Science

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