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

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.

• Authors: Dina Preise, Roni Oren, Itai Glinert, Vyacheslav Kalchenko, Steffen Jung, Avigdor Scherz, Yoram Salomon
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 58 Issue 1 Pg. 71-84 (Jan 2009) ISSN: 1432-0851 [Electronic] Germany
• PMID: 18488222 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacteriochlorophylls
• Photosensitizing Agents
• Interferon-gamma
• padeliporfin

Topics

• Animals
• Antibody Formation (drug effects)
• Bacteriochlorophylls (pharmacology)
• Blood Vessels (drug effects)
• Cell Line, Tumor
• Dendritic Cells (drug effects, immunology)
• Female
• Flow Cytometry
• Immunity, Cellular (drug effects)
• Immunohistochemistry
• Interferon-gamma (biosynthesis)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasms (drug therapy, immunology)
• Photochemotherapy
• Photosensitizing Agents (pharmacology)
• T-Lymphocytes (drug effects, immunology)