The ideal cancer treatment should target both the primary tumor and the metastases with minimal toxicity. This is best accomplished by educating the body's immune system to recognize the tumor as foreign so that after the primary tumor is destroyed, distant metastases will also be eradicated. PDT may accomplish this feat and stimulate long-term, specific anti-tumor immunity. PDT causes an acute inflammatory response, the rapid induction of large amounts of necrotic and apoptotic tumor cells, induction of immunostimulatory heat-shock proteins, tumor antigen presentation to naïve T-cells, and generation of cytotoxic T-cells that can destroy distant tumor metastases.
By using various syngeneic mouse tumors in immunocompetent mice, we can study specific PDT regimens related to tumor type as well as mouse genotype and phenotype. We have investigated the role of tumor-associated antigens in PDT-induced immune response by choosing mouse tumors that express: model defined antigen, naturally-occurring cancer testis antigen, and oncogenic virus-derived antigen.
We studied the synergistic combination of low-dose cyclophosphamide and PDT that unmasks the PDT-induced immune response by depleting the immunosuppressive T-regulatory cells. PDT combined with immunostimulants (toll-like receptor ligands) can synergistically maximize the generation of anti-tumor immunity by activating dendritic cells and switching immunosuppressive macrophages to a tumor rejection phenotype. Tumors expressing defined tumor-associated antigens with known MHC class I peptides allows anti-tumor immunity to be quantitatively compared.
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Castano AP and Hamblin MR. Enhancing photodynamic therapy of a metastatic mouse breast cancer by immune stimulation. Proc SPIE, 2006; Vol 6087. art. no. 608703.
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Mroz P, Hamblin MR. Photodynamic therapy stimulates anti-tumor immunity in a murine mastocytoma model. In: Chen WR, Editor; Biophotonics and Immune Responses III, Bellingham, WA, The International Society for Optical Engineering, Proc SPIE 6847, 2008.
Castano AP, Mroz P, Wu MX, Hamblin MR. Photodynamic therapy plus low-dose cyclophosphamide generates antitumor immunity in a mouse model. Proc Natl Acad Sci USA, 2008,105(14):5495-5500.
Mroz P, Castano AP, Hamblin MR. Stimulation of dendritic cells enhances immune response after photodynamic therapy. Proc SPIE 2009 in press
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Mroz P, Yaroslavsky A, Kharkwal GB, Hamblin MR. Cell Death Pathways in Photodynamic Therapy of Cancer. Cancers 2011, 3, 2516-2539.