Comparison of glioma-associated antigen peptide-loaded versus autologous tumor lysate-loaded dendritic cell vaccination in malignant glioma patients.
Comparison of glioma-associated antigen peptide-loaded versus autologous tumor lysate-loaded dendritic cell vaccination in malignant glioma patients.
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DOI：
10.1097/cji.0b013e3182811ae4
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
Liau LM
中科院分区：
文献类型：
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作者：
Prins RM;Wang X;Soto H;Young E;Lisiero DN;Fong B;Everson R;Yong WH;Lai A;Li G;Cloughesy TF;Liau LM
树突状细胞(DC)疫苗正在成为恶性胶质瘤患者的一种很有前途的治疗选择。然而，负载这些细胞的最佳抗原配方尚未确定。本研究的目的是比较两种不同DC疫苗接种方案对恶性胶质瘤患者的安全性、可行性和免疫应答。28例患者接受自体肿瘤裂解物(ATL)冲击的DC疫苗治疗，6例患者接受胶质瘤相关抗原(GAA)多肽冲击的DC治疗。比较每个试验患者之间的安全性、毒性、可行性和相关免疫监测结果。由于GAA-DC试验的人类白细胞抗原亚型限制，6/15名筛选的患者有资格接受治疗，而28/32名患者通过了ATL-DC试验的资格筛选。GAA-DC患者外周血中活化的自然杀伤(NK)细胞频率高于ATL-DC患者。此外，在两个试验中，患者的调节性T淋巴细胞(Treg)比率(接种后/接种前)与总存活率(OS；p=0.004)之间存在显著的相关性。事实上，在这些患者中，Treg比率是OS的独立预后因素，而肿瘤病理并不在多因素分析中。总之，这些结果表明，与GAA-DC疫苗相比，ATL-DC疫苗接种与更广泛的患者资格相关。在两个试验中，免疫后/接种前Treg比率的降低和激活的NK细胞频率的降低与患者的存活时间延长有关，这表明这些淋巴细胞亚群可能是恶性胶质瘤患者免疫治疗的相关免疫监测终点。
Dendritic cell (DC) vaccination is emerging as a promising therapeutic option for malignant glioma patients. However, the optimal antigen formulation for loading these cells has yet to be established. The objective of this study was to compare the safety, feasibility, and immune responses of malignant glioma patients on two different DC vaccination protocols. 28 patients were treated with autologous tumor lysate (ATL)-pulsed DC vaccination, while 6 patients were treated with glioma-associated antigen (GAA) peptide-pulsed DCs. Safety, toxicity, feasibility and correlative immune monitoring assay results were compared between patients on each trial. Due to HLA subtype restrictions on the GAA-DC trial, 6/15 screened patients were eligible for treatment, while 28/32 patients passed eligibility screening for the ATL-DC trial. Elevated frequencies of activated natural killer (NK) cells were observed in the peripheral blood from GAA-DC patients compared with the ATL-DC patients. In addition, a significant correlation was observed between decreased regulatory T lymphocyte (Treg) ratios (post/pre vaccination) and overall survival (OS; p=0.004) in patients on both trials. In fact, Treg ratios were independently prognostic for OS in these patients, while tumor pathology was not in multivariate analyses. In conclusion, these results suggest that ATL-DC vaccination is associated with wider patient eligibility compared with GAA-DC vaccination. Decreased post/pre-vaccination Treg ratios and decreased frequencies of activated NK cells were associated with prolonged survival in patients from both trials, suggesting that these lymphocyte subsets may be relevant immune monitoring endpoints for immunotherapy protocols in malignant glioma patients.