13 February 2007 Photodynamic therapy stimulates anti-tumor immunity in a murine model
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Cancer is a leading cause of death among modern peoples largely due to metastatic disease. The ideal cancer treatment should target both the primary tumor and the metastases with the 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. Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. We here report on PDT of mice bearing tumors that either do or do not express an established TAA. We utilized a BALB/c colon adenocarcinoma cell line termed CT26.CL25 retrovirally transduced to stably express &bgr;-galactosidase ( &bgr;-gal, a bacterial protein), and its non-&bgr;-gal expressing wild-type counterpart termed CT26 WT, as well as the control cell line consisting of CT26 transduced with the empty retroviral vector termed CT26-neo. All cells expressed class I MHC restriction element H-2Ld syngenic to BALB/c mice. Vascular PDT with a regimen of 1mg/kg BPD injected IV, and 120 J/cm2 of 690-nm laser light after 15 minutes successfully cured 100% of CT26.CL25 tumors but 0% of CT26-neo tumors and 0% of CT26 WT tumors. After 90 days tumor free interval the CT26.CL25 cured mice were rechallenged with CT26.CL25 tumor cells and 96% rejected the rechallenge while the CT26.CL25 cured mice did not reject a CT26 WT tumor cell challenge. Experiments with mice bearing two CT26.CL25 tumors (one in each leg) and only one tumor treated with PDT, showed that the immune response was strong enough to destroy an already established tumor in 70 of the mice and this effect was not seen with mice bearing two CT26 WT tumors. We expect these studies will lead to an understanding of the relevant determinants of immune response after PDT that could be rapidly applied to patient-selection and improvement in outcome for PDT for cancer.
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Pawel Mroz, Ana P. Castano, Mei X. Wu, Andrew L. Kung, Michael R. Hamblin, "Photodynamic therapy stimulates anti-tumor immunity in a murine model", Proc. SPIE 6438, Biophotonics and Immune Responses II, 643803 (13 February 2007); doi: 10.1117/12.697630; https://doi.org/10.1117/12.697630

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