Ex Vivo Generation of Functional Immune Cells by Mitochondria-Targeted Photosensitization of Cancer Cells

  • Sean Marrache
  • Smanla Tundup
  • Donald A. Harn
  • Shanta Dhar
Part of the Methods in Molecular Biology book series (MIMB, volume 1265)

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.

Key words

Photodynamic therapy Tumor antigen Mitochondria Biodegradable nanoparticle 

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Sean Marrache
    • 1
  • Smanla Tundup
    • 2
  • Donald A. Harn
    • 2
  • Shanta Dhar
    • 3
  1. 1.NanoTherapeutics Research Laboratory, Department of ChemistryUniversity of GeorgiaAthensUSA
  2. 2.Department of Infectious DiseasesUniversity of GeorgiaAthensUSA
  3. 3.Department of ChemistryUniversity of GeorgiaAthensUSA

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