一个新的平台技术RuVaCare,一种体外抗癌疫苗,有效地打破免疫屏障,靶向癌细胞(会议报告)

L. Lilge, M. A. Munegowda, A. Mandel, R. Dumoulin-White
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摘要

即使病人有良好的免疫系统,肿瘤也会受到保护,因为肿瘤的生长是通过各种机制抑制宿主的免疫反应。它们通过产生免疫抑制细胞因子如IL-10和TGF-b,表达免疫检查点配体如程序性死亡配体1 (PDL1),并携带免疫抑制细胞如Tregs和MDSCs来保持局部微环境的免疫抑制。为了克服这些障碍,一种更强的抗肿瘤免疫反应至关重要。我们在rg2 -胶质母细胞瘤模型中评估了体外Rutherrin®-PDT治疗癌细胞的全细胞疫苗(RuVaCareTM)打破抑制屏障的效果。Rutherrin®-PDT在体外诱导胶质母细胞瘤细胞强免疫原性死亡(ICD)。RuVaCareTM上清液显示出显著较高的细胞外ATP水平,已知ATP通过诱导有效的抗肿瘤免疫反应诱导抗原提呈细胞(APCs)的募集和激活。细胞外钙钙蛋白(CRT)是ICD的标志之一;在Rutherrin®-PDT介导的细胞死亡中,其表达在85%以上的细胞中升高。hsp70在RuVaCareTM中的表达量增加了近10倍。免疫刺激因子IFNa、IL-1b和GMCSF在RuVaCareTM中高表达。在原位RG2大鼠胶质母细胞瘤模型中评估RuVaCare™的体内疗效。与未接种RuVaCare™疫苗的对照组相比,接种RuVaCare™疫苗组的生存率显著增加(2次疫苗约43%,6次疫苗约87%)。瘤内CD8+ t细胞数量的增加被证明与胶质母细胞瘤大鼠的存活率增加相关,使用RuVaCare™后CD8+ t细胞数量显著增加。
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A new platform technology RuVaCare, an extracorporeal anti-cancer vaccine is efficient in breaking immune barrier to target cancer cells (Conference Presentation)
Even though a patient has a good immune system, tumors are shielded from it, because tumors grow by suppressing the host’s immune-response by various mechanisms. They are keeping their local microenvironment immune suppressed by producing immune suppressive cytokines like IL-10 and TGF-b, express immune checkpoint ligands like Programmed Death Ligand 1 (PDL1), and harbor immune suppressive cells like Tregs and MDSCs. To overcome these barriers a stronger anti-tumour immune-response is essential. We evaluated a whole cell vaccine with extracorporeal Rutherrin®-PDT treated cancer cells (RuVaCareTM) to break the suppressive barrier in the RG2-glioblastoma model. Rutherrin®-PDT induced strong immunogenic cell death (ICD) in glioblastoma cells in-vitro. RuVaCareTM supernatants showed significantly higher level of extracellular ATP, which is known to induce recruitment of antigen presenting cells (APCs) and their activation by eliciting an effective anti-tumour immune-response. Extracellular calreticulin (CRT) is one of the hallmarks of ICD; its expression went up in more than 85% cells undergoing Rutherrin®-PDT mediated cell death. There was a close to 10 times increase in expression of HSP 70 in RuVaCareTM. Immunostimulatory cytokines IFNa, IL-1b and GMCSF expression is high in the RuVaCareTM. In-vivo efficacy of the RuVaCare™ was evaluated in orthotopic RG2 rat glioblastoma model. There was a significant increase (~43% with 2-time vaccine and 87% in the 6-time vaccine) in survival in the RuVaCare™ vaccinated groups compared to unvaccinated controls. Increased intratumoral CD8+T-cell numbers are shown to be correlated with increased survival in glioblastoma rats, with RuVaCare™ there was a significant increase in the number of CD8+T-cells.
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