Therapeutic cancer vaccine made of cancer cell-derived nanovesicles produced by oxidative stress-induced expression of damage-associated molecular pattern and filter extrusion

• Main Authors: Chin-Yi Chung, 鐘晉毅
• Other Authors: 陳賜原
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/e3ma84

碩士 === 國立中央大學 === 物理學系 === 107 === 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.