Enhancing the treatment effect on melanoma by heat shock protein 70-peptide complexes purified from human melanoma cell lines.
Enhancing the treatment effect on melanoma by heat shock protein 70-peptide complexes purified from human melanoma cell lines.
复制标题
从人黑色素瘤细胞系中纯化的热休克蛋白 70 肽复合物增强对黑色素瘤的治疗效果。
DOI：
10.3892/or.2016.4947
复制
发表时间：
2016-09
期刊：
影响因子：
4.2
通讯作者：
Ren J
中科院分区：
文献类型：
--
作者：
Gao Y;Gao W;Chen X;Cha N;Wang X;Jia X;Wang B;Ren M;Ren J
树突状细胞（DC）疫苗是目前治疗黑色素瘤最有效的方法之一。负载到DC中的抗原的免疫原性决定治疗效果。用自体抗原负载的DC疫苗治疗的患者达到最佳治疗效果。在中国，大多数黑色素瘤患者无法获得其自体抗原，因为手术后福尔马林处理肿瘤组织。在本研究中，我们从人黑色素瘤细胞系A375、A875、M21、M14、WM-35和SK-HEL-1中纯化了热休克蛋白70（HSP 70）-肽复合物（PC）。纯化产物命名为M-HSP 70-PC，并测定其免疫活性。从黑色素瘤患者（9例）的原代肿瘤细胞中纯化的自体HSP 70-PC用作对照。将这两种肿瘤抗原复合物负载到DC中，用于刺激相应患者的抗肿瘤细胞的抗肿瘤应答。M-HSP 70-PC刺激的成熟DC刺激自体T细胞分泌与自体HSP 70-PC相同水平的I型细胞因子。此外，与自体HSP 70-PC相比，M-HSP 70-PC致敏的DC诱导的CD 8 + T细胞具有相同的杀伤患者黑素瘤细胞的能力。接下来，我们使用这些PC脉冲的自体DC并诱导自体特异性CD 8 + T细胞来治疗一名患有鼻皮肤黑色素瘤和肺转移的患者。治疗6个周期后取得良好效果。这些发现为不能获得自体抗原的黑色素瘤患者的基于DC的免疫治疗提供了新的方向。
Dendritic cell (DC) vaccines are currently one of the most effective approaches to treat melanoma. The immunogenicity of antigens loaded into DCs determines the treatment effects. Patients treated with autologous antigen-loaded DC vaccines achieve the best therapeutic effects. In China, most melanoma patients cannot access their autologous antigens because of formalin treatment of tumor tissue after surgery. In the present study, we purified heat shock protein 70 (HSP70)-peptide complexes (PCs) from human melanoma cell lines A375, A875, M21, M14, WM-35, and SK-HEL-1. We named the purified product as M-HSP70-PCs, and determined its immunological activities. Autologous HSP70-PCs purified from primary tumor cells of melanoma patients (nine cases) were used as controls. These two kinds of tumor antigenic complexes loaded into DCs were used to stimulate an antitumor response against tumor cells in the corresponding patients. Mature DCs pulsed with M-HSP70-PCs stimulated autologous T cells to secrete the same levels of type I cytokines compared with the autologous HSP70-PCs. Moreover, DCs pulsed with M-HSP70-PCs induced CD8+ T cells with an equal ability to kill melanoma cells from patients compared with autologous HSP70-PCs. Next, we used these PC-pulsed autologous DCs and induced autologous specific CD8+ T cells to treat one patient with melanoma of the nasal skin and lung metastasis. The treatment achieved a good effect after six cycles. These findings provide a new direction for DC-based immunotherapy for melanoma patients who cannot access autologous antigens.