Image-guided Interventional Combination Liver Cancer Immunotherapy

项目总结 对于临床应用，基于自然杀伤(NK)细胞的过继转移的关键剩余障碍 免疫治疗(ATI)是指体外扩增的效应器NKs对靶点的归巢效率不足。 肿瘤组织。另一个重大障碍是缺乏成熟的非侵入性工具来监测NK 细胞向肿瘤组织的运输。目前，基于NK细胞的ATI(NK-ATI)应答者或无应答者为 通过血清生物标记物或肿瘤大小的变化来识别，这两者可能要到几周或几个月才会发生 治疗开始后。在ATI期间对NK细胞向肿瘤的迁移进行连续监测也可以作为替代 一个重要的早期生物标志物，用于及时预测纵向反应，从而提供早期调整 每个患者的治疗方案。 最近，我们的研究表明，索拉非尼不仅可以抑制肿瘤细胞的增殖，而且还可以 促进NKs的抗肿瘤活性。因此，同时服用索拉非尼可能对 持续的NK激活和细胞毒作用。 我们研制了可生物降解的索拉非尼洗脱微球(SEM)，直径为492±34 nm； 通过图像引导经导管显著提高治疗效果的纳米扫描电子显微镜)输送平台 IHA送货。我们将开发一种新的图像引导介入联合肝癌免疫治疗 方法包括a)图像引导下经导管将NKs直接输注到靶向血供的IHA 肝肿瘤(S)和b)同时输注纳米SEMS以提高索拉非尼的疗效(以最小剂量 副作用)，增强NK抗肿瘤活性。

PROJECT SUMMARY For clinical application, a critical remaining hurdle for natural killer (NK) cell-based adoptive transfer immunotherapy (ATI) is the inadequate homing efficiency of ex vivo-expanded effector NKs to the targeted tumor tissues. Another significant obstacle is the lack of well-established non-invasive tools for monitoring NK cell trafficking to tumor tissues. Currently, NK cell-based ATI (NK-ATI) responders or non-responders are identified by changes in serum biomarkers or tumor size, both of which may not occur until weeks or months after therapy initiation. Serial monitoring of NK cell migration to tumors during ATI could alternatively serve as an important early biomarker for timely prediction of longitudinal response, thus affording early adjustments to each individual patient’s therapeutic regimen. Recently, our studies have demonstrated that sorafenib not only inhibits tumor cell proliferation, but also promotes antitumor activity of NKs. Therefore, concurrent administration of sorafenib may be critical for sustained NK activation and cytotoxicity. We have developed biodegradable sorafenib-eluting microsphere (SEM, with a diameter of 492 ± 34 nm; nano-SEM) delivery platforms that significantly increase therapeutic efficacy via image-guided transcatheter IHA delivery. We will develop a new image-guided interventional combination liver cancer immunotherapy approach including a) image-guided transcatheter IHA infusion of NKs directly into the blood supply of targeted liver tumor(s) and b) concurrent infusion of nano-SEMs to enhance sorafenib therapeutic efficacy (with minimal side effects) and to strengthen NK antitumor activity.