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Split-dose photodynamic therapy: Optimizing cures while preventing disseminated tumors.

机译：分剂量光动力疗法：在防止扩散性肿瘤的同时优化治疗方法。

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摘要

Photodynamic therapy (PDT) is an FDA approved treatment for a number of malignant and non-malignant conditions in humans. Previous pre-clinical work in murine tumor models has shown that low-inflammation ( high-fluence) PDT regimens are more effective in obtaining cure of the primary tumor but induce minimal memory anti-tumor immune response. On the contrary, high-inflammation (low-fluence) PDT regimens confer durable anti-tumor immunity but generate significantly lower cures. We proposed that an optimum split-dose PDT regimen could be designed that would enable cure of primary tumor while preventing disseminated disease via induction of anti-tumor immunity.;Four experimental groups were defined using a murine tumor model Colon 26 transfected with hemagglutinin cDNA (CT 26-HA). Controls received only the photosensitizer, a second group was given high-inflammation PDT and a third group received low-inflammation PDT. The fourth group was retreated with low-inflammation PDT seven days after initial treatment with high-inflammation PDT. Analysis of tumor responses showed only slightly higher cure rates (∼40%) with split-dose PDT compared to mice receiving only high-inflammation PDT (∼20%). However, it was noticed that there was a delay in progression of tumor growth with split-dose PDT. The experimental parameters were then modified and the split-dose gap was increased to ten days. This resulted in significantly higher cure rates (∼60%). All cured mice were re-challenged with tumor cells intra-dermally, sixty days after cure. The results exhibit a trend similar to that seen in tumor response experiments---ten day split-dose PDT regimen confers a degree of anti-tumor protection comparable to high-inflammation PDT alone, whereas seven day split dose PDT regimen does not.;Enhancement of anti-tumor immunity by high-inflammation PDT regimen is accompanied by increased cellularity of tumor draining lymph nodes and activation of tumor specific T cells. Split-dose PDT regimens also lead to enhanced T cell activation as measured by increased expression of the early T-cell activation marker CD25; interestingly CD69 expression, a second activation marker for T cells, was not increased.;We have concluded from the results that ten-day split-dose PDT regimen enables significantly higher cure rates compared to high-inflammation PDT while maintaining the anti-tumor efficacy, as evidenced by resistance to subsequent tumor re-challenges.;The results of our experiments indicate that the split-dose PDT regimen has the potential of being introduced as a useful therapeutic option in the clinical practice of PDT as it has exhibited the ability to target distant disease via activation of host immune defenses while successfully ablating the primary tumor.
机译：光动力疗法（PDT）是FDA批准的针对人类多种恶性和非恶性疾病的治疗方法。先前在鼠类肿瘤模型中进行的临床前研究表明，低炎症（高通量）PDT方案在治愈原发性肿瘤方面更有效，但诱导的记忆抗肿瘤免疫反应最小。相反，高炎症（低通量）PDT疗法具有持久的抗肿瘤免疫力，但治愈率却大大降低。我们提出了一种最佳的分剂量PDT方案，该方案可以设计为能够治愈原发性肿瘤，同时通过诱导抗肿瘤免疫力来预防弥漫性疾病。;使用转染了血凝素cDNA的鼠类肿瘤模型Colon 26定义了四个实验组（ CT 26-HA）。对照组仅接受光敏剂，第二组给予高炎症PDT，第三组接受低炎症PDT。第四组在高炎症PDT初始治疗后7天接受低炎症PDT治疗。肿瘤反应分析表明，与仅接受高炎症PDT的小鼠（约20％）相比，分剂量PDT的治愈率（约40％）略高。然而，已经注意到，分剂量PDT使肿瘤生长的进展延迟。然后修改实验参数，并将分剂量间隔增加至十天。这导致明显更高的治愈率（〜60％）。治愈后六十天，所有治愈的小鼠皮内再次受到肿瘤细胞的攻击。结果显示出与肿瘤反应实验相似的趋势-十天分剂量PDT方案可提供与单独的高炎症PDT相当的抗肿瘤保护程度，而七天分剂量PDT方案则不能。高炎症PDT方案增强抗肿瘤免疫力的同时，引流淋巴结的细胞增多，肿瘤特异性T细胞活化。按早期T细胞活化标记CD25的表达增加来衡量，分剂量的PDT疗法还可以增强T细胞活化。有趣的是，CD69表达（T细胞的第二个激活标记）并未增加。；我们从结果得出结论：与高炎症PDT相比，十天分剂量PDT方案可以显着提高治愈率，同时保持抗肿瘤功效实验结果表明，分剂量PDT方案具有显示PDT的能力，因此有可能被引入PDT的临床实践中作为一种有用的治疗选择。通过激活宿主免疫防御系统靶向远距离疾病，同时成功消融原发性肿瘤。

著录项

  • 作者

    Shams, Madeeha.;

  • 作者单位

    State University of New York at Buffalo.;

  • 授予单位 State University of New York at Buffalo.;
  • 学科 Health Sciences Occupational Therapy.;Biophysics General.;Health Sciences Oncology.
  • 学位 M.S.
  • 年度 2012
  • 页码 68 p.
  • 总页数 68
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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