RNA-transfected CD40-activated B cells induce functional T-cell responses against viral and tumor antigen targets: implications for pediatric immunotherapy
RNA-transfected CD40-activated B cells induce functional T-cell responses against viral and tumor antigen targets: implications for pediatric immunotherapy
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DOI：
10.1182/blood-2003-07-2379
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发表时间：
2004-03-15
期刊：
影响因子：
20.3
通讯作者：
Vonderheide, RH
中科院分区：
文献类型：
--
作者：
Coughlin, CM;Vance, BA;Vonderheide, RH
用抗原呈递细胞（APC）进行疫苗接种以模拟免疫刺激机制代表了癌症免疫治疗的有希望的方法。树突状细胞疫苗已进入成人恶性肿瘤的3期试验，但此类疫苗在儿童中的应用有限。我们证明，CD 40-活化的B细胞（CD 40-B）转染的RNA可以作为一种替代疫苗，可以产生从小。无论患者年龄大小，来自儿科患者的CD 40-B是有效的APC，并且可以负载RNA作为抗原有效载荷，允许同时靶向多个抗原表位而不需要HLA匹配。对于病毒和肿瘤抗原，CD 40-B/ RNA技术诱导成人和儿童的细胞毒性T淋巴细胞（CTL），其可以用肽/主要组织相容性复合物（MHC）四聚体鉴定。这些CTL分泌干扰素-γ（IFN-γ）并以MHC限制的方式杀死靶标。对于合并的神经母细胞瘤RNA和自体神经母细胞瘤RNA，产生裂解神经母细胞瘤细胞系的CTL，包括特异性针对广泛表达的肿瘤抗原存活素的CTL。这些发现为儿科恶性肿瘤的肿瘤特异性疫苗或过继免疫治疗提供了新的平台。(C)2004年，美国血液学会。
Vaccination with antigen-presenting cells (APCs) engineered to mimic mechanisms of immune stimulation represents a promising approach for cancer immunotherapy. Dendritic cell vaccines have entered phase 3 testing in adult malignancies, but such vaccines in children have been limited. We demonstrate that CD40-activated B cells (CD40-B) transfected with RNA may serve as an alternative vaccine that can be generated from small. blood volumes regardless of patient age. CD40-B from pediatric patients are efficient APCs and can be loaded with RNA as an antigenic payload, permitting simultaneous targeting of multiple antigenic epitopes without the necessity of HLA matching. For viral and tumor antigens, CD40-B/ RNA technology induced cytotoxic T lymphocytes (CTLs) from adults and children, which could be identified with peptide/major histocompatibility complex (MHC) tetramers. These CTLs secreted interferon-gamma (IFN-gamma) and killed targets in an MHC-restricted fashion. For pooled neuroblastoma RNA and autologous neuroblastoma RNA, CTLs that lysed neuroblastoma cell lines, including CTLs specific against the widely expressed tumor-antigen survivin, were generated. These findings support a novel platform for tumor-specific vaccine or adoptive immunotherapies in pediatric malignancies. (C) 2004 by The American Society of Hematology.