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Systemic antitumor protection by vascular-targeted photodynamic therapy involves cellular and humoral immunity

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Abstract

Vascular-targeted photodynamic therapy (VTP) takes advantage of intravascular excitation of a photosensitizer (PS) to produce cytotoxic reactive oxygen species (ROS). These ROS are potent mediators of vascular damage inducing rapid local thrombus formation, vascular occlusion, and tissue hypoxia. This light-controlled process is used for the eradication of solid tumors with Pd-bacteriochlorophyll derivatives (Bchl) as PS. Unlike classical photodynamic therapy (PDT), cancer cells are not the primary target for VTP but instead are destroyed by treatment-induced oxygen deprivation. VTP initiates acute local inflammation inside the illuminated area accompanied by massive tumor tissue death. Consequently, in the present study, we addressed the possibility of immune response induction by the treatment that may be considered as an integral part of the mechanism of VTP-mediated tumor eradication. The effect of VTP on the host immune system was investigated using WST11, which is now in phase II clinical trials for age-related macular degeneration and intended to be evaluated for cancer therapy. We found that a functional immune system is essential for successful VTP. Long-lasting systemic antitumor immunity was induced by VTP involving both cellular and humoral components. The antitumor effect was cross-protective against mismatched tumors, suggesting VTP-mediated production of overlapping tumor antigens, possibly from endothelial origin. Based on our findings we suggest that local VTP might be utilized in combination with other anticancer therapies (e.g., immunotherapy) for the enhancement of host antitumor immunity in the treatment of both local and disseminated disease.

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Acknowledgments

The authors wish to thank Prof. L. Eisenbach and Dr. E. Tzehoval for valuable discussions and technical help, to Dr. Ori Brener for histopathology work, to Ester Shai, for her technical help. Study supported by STEBA-BIOTECH (France).

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Authors and Affiliations

  1. Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel

    Dina Preise, Roni Oren, Itai Glinert & Yoram Salomon

  2. Department of Plant Science, The Weizmann Institute of Science, Rehovot, Israel

    Avigdor Scherz

  3. Department of Chemical Immunology, The Weizmann Institute of Science, Rehovot, Israel

    Steffen Jung

  4. Department of Veterinary Resources, The Weizmann Institute of Science, Rehovot, Israel

    Vyacheslav Kalchenko

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  1. Dina Preise
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Correspondence to Yoram Salomon.

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Y.S. and A.S are the incumbents of the Tillie and Charles Lubin Professorial Chair in Biochemical Endocrinology, and the Robert and Yaddele Sklare Professorial Chair in Biochemistry, respectively. S.J. is the incumbent of the Pauline Recanati Career Development Chair. D.P. in partial fulfillment of her PhD Thesis requirements at the Feinberg graduate school of the Weizmann Institute of Science.

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Preise, D., Oren, R., Glinert, I. et al. Systemic antitumor protection by vascular-targeted photodynamic therapy involves cellular and humoral immunity. Cancer Immunol Immunother 58, 71–84 (2009). https://doi.org/10.1007/s00262-008-0527-0

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