Chapter title |
Ex vivo generation of functional immune cells by mitochondria-targeted photosensitization of cancer cells.
|
---|---|
Chapter number | 9 |
Book title |
Mitochondrial Medicine
|
Published in |
Methods in molecular biology, January 2015
|
DOI | 10.1007/978-1-4939-2288-8_9 |
Pubmed ID | |
Book ISBNs |
978-1-4939-2287-1, 978-1-4939-2288-8
|
Authors |
Sean Marrache, Smanla Tundup, Donald A Harn, Shanta Dhar, Donald A. Harn, Marrache, Sean, Tundup, Smanla, Harn, Donald A., Dhar, Shanta |
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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