結合以氧化應激誘發癌細胞表現損傷相關分子與過濾擠壓法來生產癌細胞衍生奈米囊泡以製作治療性癌症疫苗;Therapeutic cancer vaccine made of cancer cell-derived nanovesicles produced by oxidative stress-induced expression of damage-associated molecular pattern and filter extrusion

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题名:	結合以氧化應激誘發癌細胞表現損傷相關分子與過濾擠壓法來生產癌細胞衍生奈米囊泡以製作治療性癌症疫苗;Therapeutic cancer vaccine made of cancer cell-derived nanovesicles produced by oxidative stress-induced expression of damage-associated molecular pattern and filter extrusion
作者:	鐘晉毅;Chung, Chin-Yi
贡献者:	物理學系
关键词:	奈米囊泡;損傷相關分子模式;低溫氣壓式電漿;光動力療法;過濾擠壓法;Nanovesicle;Damage-associated molecular patterns;Cold atmospheric plasma jet;Photodynamic therapy;Filter extrusion
日期:	2019-01-30
上传时间:	2019-04-02 14:33:18 (UTC+8)
出版者:	國立中央大學
摘要:	基於使用光動力療法（PDT）製備的癌症疫苗在動物實驗模型中，已被證實是治療癌症更有效的方法相較於其他癌細胞所衍生的癌症疫苗。似乎是由於光動力療法處理後的癌細胞產生高表現的熱休克蛋白70(HSP70)或其他與氧化應激誘導的損傷相關分子模式(DAMPs)，藉此所衍生的細胞膜奈米囊泡和細胞碎片使其效果更佳。為了開發出更具有治療潛力的癌症疫苗，從此實驗做延伸，我們使用不同氧化應激處理的方法去製備癌症疫苗，包括光動力療法使用標靶細胞不同位置的光敏藥劑、外加入H2O2應激處理和使用低溫氣壓式電漿（CAP）流應激處理。此外，我們將氧化應激處理後的癌細胞，使用過濾擠壓法(Filter Extrusion)產生奈米囊泡來製備癌症疫苗。藉由檢測癌症疫苗激活巨噬細胞產生一氧化氮(NO)濃度的測試、癌症疫苗激活的巨噬細胞與癌細胞共培養的毒殺測試。發現使用過濾擠壓法所產生的奈米囊泡通常比細胞自發性釋放的奈米囊泡更有效果。此外，與其他氧化應激源相比，使用低溫氣壓式電漿流處理所產生的疫苗是最有效的。結合低溫氣壓式電漿流處理以及過濾擠壓法所製備的癌症疫苗最具有治療癌症的潛力。;Photodynamic therapy (PDT)-based cancer vaccine has been shown to be a more effective modality for treating cancer in animal models compared to other methods used to generate therapeutic cancer cell-derived vaccines. The higher efficacy seems to result from the generation of cell membrane nanovesicles or fragments that carry both cancer cell-specific antigens and a high surface content of HSP70 or other damage-associated molecular pattern molecules induced by oxidative stress. Aiming to develop more effective cancer vaccine along this direction, we explored cancer vaccines generated using different sources of oxidative stress, including photosensitizers that target different parts of the cells, externally added H2O2, and cold atmospheric plasma (CAP) jet. Furthermore, we explored cancer vaccines generated by using filter extrusion to produce nanovesicles from cancer cells after oxidative stress treatment. Through the tests of activating macrophages to secret NO, killing of cancer cells by co-cultured macrophages primed by the vaccines, and animal test, it is found that the vaccine based on nanovesicles generated by filter extrusion was generally more effective than that by spontaneous release of nanovesicles. In addition, the vaccine generated by using CAP jet treatment was the most effective compared to other sources of oxidative stress. The combination of CAP jet treatment and filter extrusion resulted in a vaccine that could lead to a total regression of the tumor in the mouse model, promising for human test.
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