In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 101, No. 14 ( 2004-04-06), p. 4990-4995
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0400880101
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2004
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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