文章基本信息

标题：Melanoma cells transfected to express CD83 induce antitumor immunity that can be increased by also engaging CD137
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作者：Shilin Yang ; Yi Yang ; John Raycraft 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：14
页码：4990-4995
DOI：10.1073/pnas.0400880101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Interactions between CD83 and its ligand(s) can up-regulate immune responses. M2-CD83 cells, derived by transfecting the M2 clone of mouse melanoma K1735 cells to express mouse CD83, were rejected by syngeneic mice, unless they were injected with a CD83Ig fusion protein. Rejection was mediated by CD4+ and CD8+ T cells plus natural killer cells, whereas rejection of M2-1D8 cells, which express anti-CD137 single-chain variable region fragments (scFv), occurs in the absence of CD8+ T cells. Furthermore, the tumor specificity of the immunity induced by the two cell lines differed. Immunization with live or mitomycin C-treated M2-CD83 cells prevented outgrowth of transplanted M2-WT cells and had therapeutic efficacy against established M2-WT tumors. A highly metastatic clone of K1735 cells, SW1-C, and its subline SW1-P2, which expresses an activating transcription factor 2-driven peptide, were then studied because they have particularly low immunogenicity. Neither SW1-C nor SW1-P2 cells became rejectable after expression of CD83 or anti-CD137 scFv. However, outgrowth of cells from either line was delayed in mice immunized against M2-CD83 or M2-1D8 cells, and immunization with a mixture of mitomycin C-treated cells from M2-CD83 plus M2-1D8 prevented tumor formation by SW1-P2 cells in five of five and by SW1-C cells in three of five mice. We conclude that M2 cells expressing CD83 can induce a tumor-destructive immune response also against SW1 cells and that this response can be made more effective by combining them with M2 cells expressing anti-CD137 scFv. A similar approach may be therapeutically beneficial against certain human cancers.
关键词：tumor vaccines ; immunotherapy ; antigen presentation ; activating transcription factor 2