Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine.
Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine.
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发表时间：
2001-09
期刊：
影响因子：
11.2
通讯作者：
J. Banchereau;A. Palucka;M. Dhodapkar;S. Burkeholder;Nicolas Taquet;Alexandre Rolland;Sybil Taquet;Sebastien Coquery;K. Wittkowski;N. Bhardwaj;L. Piñeiro;R. Steinman;J. Fay
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作者：
J. Banchereau;A. Palucka;M. Dhodapkar;S. Burkeholder;Nicolas Taquet;Alexandre Rolland;Sybil Taquet;Sebastien Coquery;K. Wittkowski;N. Bhardwaj;L. Piñeiro;R. Steinman;J. Fay
迄今为止，已经证明对多种确定的肿瘤抗原进行免疫以用于人类癌症的特异性免疫治疗是困难的。18名患有转移性黑色素瘤的HLA A*0201（+）患者接受皮下注射。CD 34（+）祖细胞来源的自体树突状细胞（DC），其中包括朗格汉斯细胞。用衍生自四种黑素瘤抗原[（MelAgs）MelanA/MART-1、酪氨酸酶、法师-3和gp 100]的肽以及作为对照抗原的流感基质肽（Flu-MP）和钥孔血蓝蛋白（KLH）脉冲DC。通过使用边际似然评分比较应答特征来评估总体免疫学效应。DC注射耐受性良好，除了两名患者的进行性白癜风。在18名患者中的16名中，DC诱导了对对照抗原（KLH，Flu-MP）的免疫应答。在这16名患者中，观察到对一种或多种MelAgs的免疫反应增强，其中包括10名对>2种MelAgs有反应的患者。对对照和肿瘤抗原均无应答的两名患者经历了快速肿瘤进展。在17名具有可评估疾病的患者中，7名对两种或更少MelAg具有免疫力的患者中有6名在进入研究后10周具有进展性疾病，与之形成对比的是，10名对>2种MelAg具有免疫力的患者中仅1名具有肿瘤进展。在这些患者中的7名中观察到>1个肿瘤转移的消退。DC疫苗接种后对MelAgs的总体免疫与临床结果相关（P = 0.015）。
Immunization to multiple defined tumor antigens for specific immune therapy of human cancer has thus far proven difficult. Eighteen HLA A*0201(+) patients with metastatic melanoma received injections s.c. of CD34(+)progenitor-derived autologous dendritic cells (DCs), which included Langerhans cells. DCs were pulsed with peptides derived from four melanoma antigens [(MelAgs) MelanA/MART-1, tyrosinase, MAGE-3, and gp100], as well as influenza matrix peptide (Flu-MP) and keyhole limpet hemocyanin (KLH) as control antigens. Overall immunological effects were assessed by comparing response profiles using marginal likelihood scores. DC injections were well tolerated except for progressive vitiligo in two patients. DCs induced an immune response to control antigens (KLH, Flu-MP) in 16 of 18 patients. An enhanced immune response to one or more MelAgs was seen in these same 16 patients, including 10 patients who responded to >2 MelAgs. The two patients failing to respond to both control and tumor antigens experienced rapid tumor progression. Of 17 patients with evaluable disease, 6 of 7 patients with immunity to two or less MelAgs had progressive disease 10 weeks after study entry, in contrast to tumor progression in only 1 of 10 patients with immunity to >2 MelAgs. Regression of >1 tumor metastases were observed in seven of these patients. The overall immunity to MelAgs after DC vaccination is associated with clinical outcome (P = 0.015).