10021-IMT-1 A ROLE OF DENDRITIC CELL IMMUNOTHERAPY AS A MODALITY IN MULTIDISCIPLINARY THERAPY FOR GLIOBLASTOMA

Y. Akasaki, Jun Takei, Yohei Yamamoto, Toshihide Tanaka, A. Teshigawara, Yuko Kamata, Keiichiro Ohara, Shohei Nawate, Tomoya Suzuki, Takaaki Yanagisawa, Yuichi Murayama
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Abstract

Abstract We are conducting a clinical study of immunotherapy using tumor-fused dendritic cells (TFDC) as a modality of multidisciplinary treatment for patients with glioblastoma (GBM). In this study, we analyzed the additional effect of TFDC-immunotherapy for standard therapy. Newly diagnose GBM patients who treated at four of Jikei University Hospitals were analyzed in this study. Adjuvant therapy after tumor removal surgery was maintained according to the Supp's regimen. Bevacizumab (10 mg/kg, every 2 weeks) was added when a recurred tumor was confirmed. TFDC vaccine was generated from cultured tumor cells derived from autologous surgical specimen and dendritic cells from peripheral blood, and were subcutaneously administered in the cervical region for 3-14 times. All patients who had not participated in any other immunotherapy-related clinical studies were compared as a control group in a Propensity score matching analysis. The number of analyzed patients was 55 in the immunotherapy group and 35 in the control group. The 2-year survival rate and 5-year survival rate were 20.9% and 0% in the control group, respectively, while the immunotherapy group was 45.7% and 22.7%, respectively. A statistically significant difference in overall survival was observed between them (p=0.0045). There was no difference in the observed adverse events in the two groups. Specific adverse events for TFDC-immunotherapy was not observed. In the biomarker analysis, low HLA-A expression and lack of CCDC88A, KRT4, TACC2, and TONSL mutations in tumor cells were suggested as biomarkers of better prognosis. We are currently analyzing IDH profile in those patients for further analysis. TFDC-immunotherapy should be adopted as one of the modality of multidisciplinary treatments for GBM because it is expected to have some additional effects for standard therapeutic reagents without adversely affecting them. Since there are a certain number of poor responders for this immunotherapy, predictive biomarkers of therapeutic efficacy are awaited.
10021-IMT-1 树突状细胞免疫疗法在胶质母细胞瘤多学科疗法中的作用
我们正在进行一项使用肿瘤融合树突状细胞(TFDC)作为胶质母细胞瘤(GBM)患者多学科治疗方式的免疫治疗的临床研究。在本研究中,我们分析了tfdc免疫治疗对标准治疗的额外作用。本研究分析了在志庆大学四所医院治疗的新诊断GBM患者。肿瘤切除手术后的辅助治疗按照Supp的方案进行。当确认肿瘤复发时,添加贝伐单抗(10 mg/kg,每2周)。TFDC疫苗由自体手术标本肿瘤细胞和外周血树突状细胞培养而成,皮下注射3-14次。所有未参加任何其他免疫治疗相关临床研究的患者作为对照组进行倾向评分匹配分析。免疫治疗组55例,对照组35例。对照组患者2年生存率为20.9%,5年生存率为0%,免疫治疗组患者2年生存率为45.7%,5年生存率为22.7%。两组总生存率比较,差异有统计学意义(p=0.0045)。两组观察到的不良事件无差异。未观察到tfdc免疫治疗的特异性不良事件。在生物标志物分析中,肿瘤细胞中低HLA-A表达和缺乏CCDC88A、KRT4、TACC2和TONSL突变被认为是预后较好的生物标志物。我们目前正在分析这些患者的IDH谱,以作进一步分析。由于tfdc -免疫治疗有望对标准治疗试剂产生一些额外的作用,而不会对其产生不良影响,因此应采用tfdc -免疫治疗作为GBM的多学科治疗方式之一。由于对这种免疫疗法有一定数量的不良反应,因此等待治疗效果的预测性生物标志物。
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