Retargeted human avidin-CAR T cells for adoptive immunotherapy of EGFRvIII expressing gliomas and their evaluation via optical imaging

Oncotarget. 2015 Sep 15;6(27):23735-47. doi: 10.18632/oncotarget.4362.

Abstract

There has been significant progress in the design of chimeric antigen receptors (CAR) for adoptive immunotherapy targeting tumor-associated antigens. However, the challenge of monitoring the therapy in real time has been continually ignored. To address this issue, we developed optical molecular imaging approaches to evaluate a recently reported novel CAR strategy for adoptive immunotherapy against glioma xenografts expressing EGFRvIII. We initially biotinylated a novel anti-EGFRvIII monoclonal antibody (biotin-4G1) to pre-target EGFRvIII+ gliomas and then redirect activated avidin-CAR expressing T cells against the pre-targeted biotin-4G1. By optical imaging study and bio-distribution analysis, we confirmed the specificity of pre-target and target and determined the optimal time for T cells adoptive transfer in vivo. The results showed this therapeutic strategy offered efficient therapy effect to EGFRvIII+ glioma-bearing mice and implied that optical imaging is a highly useful tool in aiding in the instruction of clinical CAR-T cells adoptive transfer in future.

Keywords: EGFRvIII; adoptive immunotherapy; avidin-CAR; biotinylated; optical imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, Neoplasm / immunology
  • Antineoplastic Agents / immunology
  • Avidin / genetics
  • Avidin / immunology
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Cell Line, Tumor
  • Cytokines / metabolism
  • ErbB Receptors / biosynthesis*
  • ErbB Receptors / genetics
  • ErbB Receptors / immunology
  • Female
  • Glioma / genetics
  • Glioma / pathology
  • Glioma / therapy*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Optical Imaging / methods*
  • Receptors, Antigen / genetics
  • Receptors, Antigen / immunology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / pharmacology*
  • T-Lymphocytes / immunology*
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Cytokines
  • Receptors, Antigen
  • Recombinant Fusion Proteins
  • epidermal growth factor receptor VIII
  • Avidin
  • ErbB Receptors