Targeted microbubbles with ultrasound irradiation and PD-1 inhibitor to increase antitumor activity in B-cell lymphoma

Nanomedicine (Lond). 2018 Feb;13(3):297-311. doi: 10.2217/nnm-2017-0296. Epub 2018 Jan 17.

Abstract

Aim: Severe cardiac toxicity of doxorubicin and an immunosuppressive tumor micro-environment become main obstacles for the effective treatment of B-cell lymphoma. In this research, rituximab-conjugated and doxorubicin-loaded microbubbles (RDMs) were designed for exploring a combination approach of targeted microbubbles with ultrasound (US) irradiation and PD-1 inhibitor to overcome obstacles mentioned above.

Methods: In vivo studies were performed on SU-DHL-4 cell-grafted mice and ex vivo studies were performed on CD20+ human SU-DHL-4 cells and human T cells.

Results: A greater therapeutic effect and higher expression of PD-L1 protein expression were obtained with RDMs with US irradiation in vivo. A significant inhibitory effect on SU-DHL-4 B-cell lymphoma cells was observed after treated by RDMs with US irradiation and PD-1 inhibitor ex vivo.

Conclusion: Combination of RDMs with US irradiation and PD-1 inhibitor could be a promising therapeutic strategy for B-cell lymphoma.

Keywords: PD-1 inhibitor; targeted microbubbles; ultrasound irradiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-H1 Antigen / immunology*
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage
  • Doxorubicin / chemistry
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / pathology
  • Mice
  • Microbubbles / therapeutic use
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology*
  • Rituximab / administration & dosage
  • Rituximab / chemistry
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / radiation effects
  • Ultrasonic Waves
  • Xenograft Model Antitumor Assays

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Rituximab
  • Doxorubicin