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.
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Acknowledgements
This work was supported by a start-up grant from the National Institutes of Health (P30 GM 092378) to UGA and by the Office of the Vice President for Research, UGA, to S.D., and a grant from the National Institutes of Health (NIH AI056484) to D.H.
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Marrache, S., Tundup, S., Harn, D.A., Dhar, S. (2015). Ex Vivo Generation of Functional Immune Cells by Mitochondria-Targeted Photosensitization of Cancer Cells. In: Weissig, V., Edeas, M. (eds) Mitochondrial Medicine. Methods in Molecular Biology, vol 1265. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2288-8_9
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DOI: https://doi.org/10.1007/978-1-4939-2288-8_9
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