PROTAC 工程化蛋白/DNA 纳米抗原是癌症免疫治疗中树突状细胞疫苗的有效增强剂
PROTAC-Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Ex vivo photothermal treatment-induced immunogenic cell death for anticancer vaccine development.
Ex vivo photothermal treatment-induced immunogenic cell death for anticancer vaccine development.
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光热疗法是一种通过将光能转化为热能诱导细胞死亡的抗癌策略。在光热疗法中,癌细胞接受光热剂(如 indocyanine green)处理,并用激光照射。癌细胞中的热应激导致细胞死亡和炎症反应。
在本研究中,我们展示了离体光热(PT)处理后的细胞如何发生免疫原性细胞死亡。PT 处理导致小鼠肿瘤细胞中热休克蛋白(HSP)27、HSP70 和 HSP90 的显著表达。为评估热应激细胞的免疫原性,将 PT 处理的肿瘤细胞或水浴加热细胞的裂解物脉冲至同基因骨髓来源的树突状细胞(DCs),以制备 DC 疫苗。给予 PT 处理的肿瘤裂解物脉冲的 DC 疫苗可显著抑制 BALB/c 和 C57BL/6 同基因荷瘤小鼠的肿瘤生长。在 HSP 抑制剂 J2、VER-155008 或 17-AAG 存在下,PT 处理癌细胞的免疫原性降低。
我们的研究阐明了 PT 技术如何具有不同于水浴加热的机制,并可能成为开发抗癌疫苗的一种潜在稳健且高效的解决方案。
Photothermal therapy is an anti-cancer strategy that induce cell death by converting light energy into heat energy. During photothermal therapy, cancer cells were treated with photothermal agents, such as indocyanine green, and irradiated with a laser. Heat stress in cancer cells results in cellular death and inflammatory responses. In the present study, we demonstrated how ex vivo photothermal (PT)-treated cells underwent immunogenic cell death. PT treatment caused significant expression of heat shock protein (HSP) 27, HSP70, and HSP90 in murine tumor cells.
To evaluate the immunogenicity of heat-stressed cells, lysate from PT-treated tumor cells or water-based heated cells was pulsed to syngeneic bone-marrow-derived dendritic cells (DCs) to generate a DC-based vaccine. Administration with PT-treated tumor lysates-pulsed DC vaccine resulted in significant inhibition of tumor growth in BALB/c and C57BL/6 syngeneic tumor-bearing mice. The immunogenicity of PT-treated cancer cells was reduced in the presence of HSP inhibitors, J2, VER-155008 or 17-AAG.
Our study elucidates how PT techniques have distinct mechanisms from water-based heating and might be a potentially robust and efficient solution to developing an anti-cancer vaccine.
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