Systemic antitumor protection by vascular-targeted photodynamic therapy involves cellular and humoral immunity
Systemic antitumor protection by vascular-targeted photodynamic therapy involves cellular and humoral immunity
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DOI：
10.1007/s00262-008-0527-0
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发表时间：
2009-01-01
影响因子：
5.8
通讯作者：
Salomon, Yoram
中科院分区：
文献类型：
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作者：
Preise, Dina;Oren, Roni;Salomon, Yoram
血管靶向光动力学疗法（Vascular-targeted photodynamic therapy，VTP）利用光敏剂（photosensitive，PS）的血管内激发来产生细胞毒性活性氧（reactive oxygen species，ROS）。这些ROS是诱导快速局部血栓形成、血管闭塞和组织缺氧的血管损伤的有效介质。该光控过程用于用Pd-细菌叶绿素衍生物（Bchl）作为PS根除实体瘤。与经典的光动力疗法（PDT）不同，癌细胞不是VTP的主要靶点，而是通过治疗诱导的缺氧而被破坏。VTP在照射区域内引发急性局部炎症，并伴有大量肿瘤组织死亡。因此，在本研究中，我们探讨了治疗诱导免疫反应的可能性，这可能被认为是VTP介导的肿瘤根除机制的一个组成部分。使用WST 11研究了VTP对宿主免疫系统的影响，WST 11目前正处于年龄相关性黄斑变性的II期临床试验中，并打算用于癌症治疗。我们发现，一个功能正常的免疫系统是成功的VTP必不可少的。长期持久的全身抗肿瘤免疫诱导的VTP涉及细胞和体液成分。抗肿瘤作用是交叉保护，对不匹配的肿瘤，提示VTP介导的重叠肿瘤抗原的生产，可能从内皮来源。根据我们的研究结果，我们建议局部VTP可以与其他抗癌疗法联合使用（例如，免疫疗法）用于在治疗局部和播散性疾病中增强宿主抗肿瘤免疫。
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.