清除Treg細(xì)胞提高SA-mGM-CSF前列腺癌細(xì)胞疫苗的抗腫瘤效果
發(fā)布時(shí)間:2022-01-26 18:50
研究背景前列腺癌是歐美國家男性最常見的惡性腫瘤之一,早期局限性前列腺癌一般采用手術(shù)或局部放療,而晚期多采用內(nèi)分泌治療,但隨著時(shí)間的延長,很多患者發(fā)展為去勢(shì)抵抗性前列腺癌。免疫治療(疫苗或細(xì)胞因子)是治療腫瘤的有效途徑之一。本實(shí)驗(yàn)將鏈親和素標(biāo)記的mGM-CSF(SA-mGM-CSF)錨定在生物素化的腫瘤細(xì)胞表面,成功制備一種新型腫瘤細(xì)胞疫苗。研究表明該疫苗具有較好的療效,但疫苗治療后腫瘤微環(huán)境中的Treg細(xì)胞也明顯增加。Treg細(xì)胞是一群具有免疫抑制功能的T細(xì)胞亞群,參與腫瘤免疫逃逸。因此,抑制或清除Treg細(xì)胞必將有效提高抗腫瘤免疫反應(yīng)。近期研究發(fā)現(xiàn),ICOS+Treg是發(fā)揮免疫抑制作用的主要Treg亞群。我們前期的研究發(fā)現(xiàn),體外活化ICOS信號(hào)可顯著促進(jìn)Treg細(xì)胞的增殖和免疫抑制功能。基于以上研究結(jié)果,我們提出設(shè)想:采用ICOS封閉性抗體靶向清除Treg細(xì)胞,從而提高疫苗的療效。去甲斑蝥素(NCTD)具有很強(qiáng)的抗腫瘤能力,能抑制多種腫瘤細(xì)胞的增殖并誘導(dǎo)其凋亡。NCTD具有區(qū)別于普通化療藥物的最顯著特點(diǎn),即NCTD具有升白作用,可減少化療后的骨髓抑制。近期有報(bào)道稱,NCTD還具有免疫...
【文章來源】:南方醫(yī)科大學(xué)廣東省
【文章頁數(shù)】:83 頁
【學(xué)位級(jí)別】:碩士
【部分圖文】:
圖1-1流式檢測(cè)SA-mGM-CSF對(duì)RM-1前列腺癌細(xì)胞的錨定率
碩士學(xué)位論文??-CSF膜修飾的滅活RM-1前列腺癌細(xì)胞疫苗聯(lián)合ICOS封閉性抗GM-CSF膜修飾的滅活RM-1前列腺癌細(xì)胞疫苗聯(lián)合IgG2b抗體-mGM-CSF膜修飾的滅活RM-1前列腺癌細(xì)胞疫苗組或MS組的相比是最小的,具有顯著性差異(F=?372.589,?P<0.01)。此部分SA-mGM-CSF膜修飾的滅活RM-1前列腺癌細(xì)胞疫苗可以有效地腫瘤免疫反應(yīng),當(dāng)疫苗和ICOS封閉性抗體聯(lián)用時(shí),機(jī)體的抗腫加顯著。????+
加到流式檢測(cè)管中,按上述流式檢測(cè)步驟用流式細(xì)胞儀分析外周血的DC細(xì)胞??的比例。使用統(tǒng)計(jì)分析軟件SPSS?19.0?(One-Way?ANOVA統(tǒng)計(jì)方法)對(duì)進(jìn)行數(shù)??據(jù)處理。分析結(jié)果表明(圖2-2-A,圖2-2-B,表2-2):與PBS組相比,疫苗治??療后DC細(xì)胞的比例明顯上升(F=75.031
【參考文獻(xiàn)】:
期刊論文
[1]B7 molecule mRNA expression in colorectal carcinoma[J]. Ju-Xiang Xiao, Pei-Song Bai, Li Li, Juan Zhu, Department of Oncology, First Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China Bao-Chang Lai, Yi-Li Wang, Institute for Cancer research, School of Life Science and Technology of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China. World Journal of Gastroenterology. 2005(36)
[2]In situ expression and significance of B7 costimulatory molecules within tissues of human gastric carcinoma[J]. Xiao-Li Chen An-Jing Kang Kang-Min Wang Bao-Shan Su Department of Pathology,Second Hospital of Xi’an Jiaotong University,Xi’an 710004,Shaanxi Provice,China Xu-Dong Cao Medical School of Shihezi University,Shihezi 832002,Xinjiang Uygur Autonomous Region,China Yi-Li Wang Institute of Immunopathology,Medical School of Xi’an Jiaotong University,Xi’an 710061,Shaanxi Provice,China. World Journal of Gastroenterology. 2003(06)
[3]Apoptosis induced by norcantharidin in human tumor cells[J]. Zhen Xiao Sun Qing Wen Ma Tian De Zhao Yu Lin Wei Guang Sheng Wang Jia Shi Li Liaocheng Teachers University,Liaocheng 252059,Shandong Province,China China-Japan Friendship Institute of Clinical Medical Sciences,Beijing 100029,China Institute of Pharmacy,Beijing Fourth Pharmaceutical Factory,Beijing 100081,China Beijing University of Traditional Chinese Madicine,Beijing 100029,China. World Journal of Gastroenterology. 2000(02)
本文編號(hào):3610995
【文章來源】:南方醫(yī)科大學(xué)廣東省
【文章頁數(shù)】:83 頁
【學(xué)位級(jí)別】:碩士
【部分圖文】:
圖1-1流式檢測(cè)SA-mGM-CSF對(duì)RM-1前列腺癌細(xì)胞的錨定率
碩士學(xué)位論文??-CSF膜修飾的滅活RM-1前列腺癌細(xì)胞疫苗聯(lián)合ICOS封閉性抗GM-CSF膜修飾的滅活RM-1前列腺癌細(xì)胞疫苗聯(lián)合IgG2b抗體-mGM-CSF膜修飾的滅活RM-1前列腺癌細(xì)胞疫苗組或MS組的相比是最小的,具有顯著性差異(F=?372.589,?P<0.01)。此部分SA-mGM-CSF膜修飾的滅活RM-1前列腺癌細(xì)胞疫苗可以有效地腫瘤免疫反應(yīng),當(dāng)疫苗和ICOS封閉性抗體聯(lián)用時(shí),機(jī)體的抗腫加顯著。????+
加到流式檢測(cè)管中,按上述流式檢測(cè)步驟用流式細(xì)胞儀分析外周血的DC細(xì)胞??的比例。使用統(tǒng)計(jì)分析軟件SPSS?19.0?(One-Way?ANOVA統(tǒng)計(jì)方法)對(duì)進(jìn)行數(shù)??據(jù)處理。分析結(jié)果表明(圖2-2-A,圖2-2-B,表2-2):與PBS組相比,疫苗治??療后DC細(xì)胞的比例明顯上升(F=75.031
【參考文獻(xiàn)】:
期刊論文
[1]B7 molecule mRNA expression in colorectal carcinoma[J]. Ju-Xiang Xiao, Pei-Song Bai, Li Li, Juan Zhu, Department of Oncology, First Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China Bao-Chang Lai, Yi-Li Wang, Institute for Cancer research, School of Life Science and Technology of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China. World Journal of Gastroenterology. 2005(36)
[2]In situ expression and significance of B7 costimulatory molecules within tissues of human gastric carcinoma[J]. Xiao-Li Chen An-Jing Kang Kang-Min Wang Bao-Shan Su Department of Pathology,Second Hospital of Xi’an Jiaotong University,Xi’an 710004,Shaanxi Provice,China Xu-Dong Cao Medical School of Shihezi University,Shihezi 832002,Xinjiang Uygur Autonomous Region,China Yi-Li Wang Institute of Immunopathology,Medical School of Xi’an Jiaotong University,Xi’an 710061,Shaanxi Provice,China. World Journal of Gastroenterology. 2003(06)
[3]Apoptosis induced by norcantharidin in human tumor cells[J]. Zhen Xiao Sun Qing Wen Ma Tian De Zhao Yu Lin Wei Guang Sheng Wang Jia Shi Li Liaocheng Teachers University,Liaocheng 252059,Shandong Province,China China-Japan Friendship Institute of Clinical Medical Sciences,Beijing 100029,China Institute of Pharmacy,Beijing Fourth Pharmaceutical Factory,Beijing 100081,China Beijing University of Traditional Chinese Madicine,Beijing 100029,China. World Journal of Gastroenterology. 2000(02)
本文編號(hào):3610995
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