Dendritic cells transduced with autoantigen FCRLA induce cytotoxic lymphocytes and vaccinate against murine B-Cell lymphoma
Dendritic cells transduced with autoantigen FCRLA induce cytotoxic lymphocytes and vaccinate against murine B-Cell lymphoma
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DOI：
10.1038/sj.jid.5700909
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发表时间：
2007-12-01
影响因子：
6.5
通讯作者：
Shimada, Shinji
中科院分区：
文献类型：
--
作者：
Inozume, Takashi;Mitsui, Hiroshi;Shimada, Shinji
我们之前报道了人类Fc受体样A(HFCRLA)的早期证据，hFCRLA是一种抗原(Ag)，在黑素细胞、黑色素瘤细胞和一些B细胞状态下特异表达，并被黑色素瘤患者的抗体识别。最近的研究表明，hFCRLA在大多数人类B细胞淋巴瘤组织中都有表达。在这篇报道中，我们研究了FCRLA作为B细胞淋巴瘤的肿瘤相关抗原用于免疫治疗的可能性。我们证实，小鼠FCRLA(MFCRLA)在小鼠组织中表达和分布与hFCRLA相似。构建含多聚精氨酸(R9)-蛋白转导结构域(rR9-HA-mFCRL)的重组mFCRLA融合蛋白，体外转导骨髓来源的树突状细胞(DC)。RR9-HA-mFCRL处理的DC免疫小鼠，可诱导细胞毒性T淋巴细胞(CTL)杀伤大量表达mFCRLA的B细胞淋巴瘤A20细胞。在一项具有肿瘤挑战性的研究中，与对照组相比，接种rR9-HA-mFCRL处理的DC的小鼠皮肤中接种的A20肿瘤生长显著受到抑制。这些结果表明，FCRLA是一种潜在的B细胞淋巴瘤免疫治疗靶抗原。此外，我们的实验系统使用包含全长蛋白的R9-PTD，可能是一种有用的方法来分析体内新的相关AGS候选的免疫原性。
We previously reported early evidence of the human Fc receptor-like A (hFCRLA), an antigen (Ag) that was specifically expressed in melanocytes, melanoma cells, and some B-cell states, and was recognized by IgG antibodies from melanoma patients. Recently, it has been demonstrated that hFCRLA is expressed in most human B-cell lymphoma tissues. In this report, we investigated the potential of FCRLA as a tumor-associated Ag of B-cell lymphoma for immunotherapy. We confirmed that murine FCRLA (mFCRLA) was expressed and distributed in murine tissues similar to hFCRLA. Recombinant mFCRLA fusion protein was constructed with a polyarginine (R9)-protein-transduction domain (PTD) (rR9-HA-mFCRL), and was transduced into bone marrow-derived dendritic cells ( DC) ex vivo. Mice immunized with rR9-HA-mFCRL-treated DC primed cytotoxic T-lymphocyte (CTL) that killed the B-cell lymphoma cell line (A20), which express mFCRLA abundantly. In a tumor challenging study, A20 tumor growth inoculated in skin was significantly suppressed in mice vaccinated with rR9-HA-mFCRL-treated DC, compared with control mice. These results indicated that FCRLA is a potential target Ag in immunotherapy for B-cell lymphoma. In addition, our experimental system using R9-PTDcontaining full-length proteins might be a useful method to analyze the immunogenicity of novel candidates of associated Ags in vivo.