Nanoparticle Targeting of Neutrophils for Improved Cancer Immunotherapy

Adv Healthc Mater. 2016 May;5(9):1088-93. doi: 10.1002/adhm.201500998. Epub 2016 Mar 17.

Abstract

Cancer immunotherapy using tumor-specific monoclonal antibodies presents a novel approach for cancer treatment. A monoclonal antibody TA99 specific for gp75 antigen of melanoma initiates neutrophil recruitment in tumor responsible for cancer therapy. Here, a strategy is reported for hijacking neutrophils in vivo using nanoparticles (NPs) to deliver therapeutics into tumor. In a mouse model of melanoma, it is shown that systemically delivered albumin NPs increase in tumor when TA99 antibody is injected; and the NP tumor accumulation is mediated by neutrophils. After the administration of pyropheophorbide-a loaded albumin NPs and TA99, photodynamic therapy significantly suppresses the tumor growth and increases mouse survival compared with treatment with the NPs or TA99. The study reveals a new avenue to treat cancer by NP hitchhiking of immune systems to enhance delivery of therapeutics into tumor sites.

Keywords: albumin nanoparticles; antibodies; immunotherapy; neutrophils; tumor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / chemistry
  • Antineoplastic Agents, Immunological / immunology
  • Antineoplastic Agents, Immunological / pharmacology*
  • Immunotherapy*
  • Mice
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use*
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / pathology
  • Neutrophil Infiltration / drug effects*
  • Neutrophil Infiltration / immunology
  • Neutrophils / immunology*

Substances

  • Antineoplastic Agents, Immunological