Ex vivo generation of functional immune cells by mitochondria-targeted photosensitization of cancer cells

Methods Mol Biol. 2015:1265:113-22. doi: 10.1007/978-1-4939-2288-8_9.

Abstract

Stimulating the immune system for potent immune therapy against cancer is potentially a revolutionary method to eradicate cancer. Tumors stimulated with photosensitizers (PSs) not only kill cancer cells but also help to boost the immune system. We recently reported that tumor-associated antigens (TAAs) generated by delivery of a mitochondria-acting PS zinc phthalocyanine (ZnPc) to MCF-7 breast cancer cells followed by laser irradiation can lead to ex vivo stimulation of mouse bone marrow-derived dendritic cells (BMDCs). The antigens generated from the breast cancer cells were also found to cause significant DC maturation and the activated DCs were able to stimulate T cells to cytotoxic CD8(+) T cells. In this protocol, we describe methods to engineer a mitochondria-targeted biodegradable nanoparticle (NP) formulation, T-ZnPc-NPs for delivery of ZnPc to the mitochondria of MCF-7 cells, subsequent photodynamic therapy (PDT) using a long wavelength laser irradiation to produce TAAs, DC stimulation by the TAAs to secrete interferon-gamma (IFN-γ), and matured DC-driven T-cell activation.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / immunology
  • Cancer Vaccines
  • Cell Line, Tumor
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Lymphocyte Activation / immunology
  • Mice
  • Mitochondria / metabolism*
  • Mitochondria / radiation effects
  • Nanoconjugates / chemistry*
  • Photochemotherapy
  • Polyethylene Glycols / chemistry
  • Polyglactin 910 / chemistry
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Nanoconjugates
  • poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer
  • Polyglactin 910
  • Polyethylene Glycols