Melanoma cells transfected to express CD83 induce antitumor immunity that can be increased by also engaging CD137.
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.
Yang
Shilin
S
Pacific Northwest Research Institute, Seattle, WA 98122, USA.
Yang
Yi
Y
Raycraft
John
J
Zhang
Hongtao
H
Kanan
Sandra
S
Guo
Yajun
Y
Ronai
Ze'ev
Z
Hellstrom
Ingegerd
I
Hellstrom
Karl Erik
KE
D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017931:DNA Primers; D005260:Female; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D010641:Phenotype; D017475:Receptors, Nerve Growth Factor / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D012878:Skin Neoplasms / Q000276:immunology*; D014162:Transfection; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D000097802:CD83 Antigen
D015703:Antigens, CD; D017931:DNA Primers; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D000097802:CD83 Antigen; C505714:TNFRSF9 protein, human; C505715:Tnfrsf9 protein, mouse