1] Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380453, Chile [2] Service of Urology, University of Chile Clinical Hospital, Santiago 8380453, Chile [3] Millennium Institute on Immunology and Immunotherapy, University of Chile, Santiago 8380453 Chile.
Br J Cancer. 2013 Sep 17;109(6):1488-97. doi: 10.1038/bjc.2013.494. Epub 2013 Aug 29.
Recently, we produced a tumour antigen-presenting cells (TAPCells) vaccine using a melanoma cell lysate, called TRIMEL, as an antigen source and an activation factor. Tumour antigen-presenting cells induced immunological responses and increased melanoma patient survival. Herein, we investigated the effect of TAPCells loaded with prostate cancer cell lysates (PCCL) as an antigen source, and TRIMEL as a dendritic cell (DC) activation factor; which were co-injected with the Concholepas concholepas haemocyanin (CCH) as an adjuvant on castration-resistant prostate cancer (CRPC) patients.
The lysate mix capacity, for inducing T-cell activation, was analysed by flow cytometry and Elispot. Delayed-type hypersensitivity (DTH) reaction against PCCL, frequency of CD8(+) memory T cells (Tm) in blood and prostate-specific antigen (PSA) levels in serum were measured in treated patients.
The lysate mix induced functional mature DCs that were capable of activating PCCL-specific T cells. No relevant adverse reactions were observed. Six out of 14 patients showed a significant decrease in levels of PSA. DTH(+) patients showed a prolonged PSA doubling-time after treatment. Expansion of functional central and effector CD8(+) Tm were detected.
Treatment of CRPC patients with lysate-loaded TAPCells and CCH as an adjuvant is safe: generating biochemical and memory immune responses. However, the limited number of cases requires confirmation in a phase II clinical trial.
最近，我们使用黑色素瘤细胞裂解物（称为 TRIMEL）作为抗原来源和激活因子，制备了一种肿瘤抗原呈递细胞（TAPCells）疫苗。肿瘤抗原呈递细胞可诱导免疫反应并提高黑色素瘤患者的生存率。在此，我们研究了负载前列腺癌细胞裂解物（PCCL）作为抗原来源的 TAPCells，以及将 TRIMEL 作为树突状细胞（DC）激活因子的效果；并用 Concholepas concholepas 血蓝蛋白（CCH）作为佐剂共同注射到去势抵抗性前列腺癌（CRPC）患者中。
通过流式细胞术和 Elispot 分析了诱导 T 细胞激活的裂解物混合物的容量。在接受治疗的患者中，测量了针对 PCCL 的迟发型超敏反应（DTH）反应、血液中 CD8(+)记忆 T 细胞（Tm）的频率和血清中前列腺特异性抗原（PSA）水平。
裂解物混合物诱导了功能成熟的 DC，能够激活 PCCL 特异性 T 细胞。未观察到相关不良反应。14 名患者中有 6 名 PSA 水平显著下降。DTH(+)患者在治疗后 PSA 倍增时间延长。检测到功能性中央和效应 CD8(+)Tm 的扩增。
用负载裂解物的 TAPCells 和 CCH 作为佐剂治疗 CRPC 患者是安全的：可产生生化和记忆免疫反应。然而，由于病例数量有限，需要在 II 期临床试验中进行确认。
