Target-specific activation of mast cells by immunoglobulin E reactive with a renal cell carcinoma-associated antigen.
Immunoglobulin E (IgE) that specifically binds to antigens present on carcinoma cells may represent a useful tool to combat carcinomas. Induction of an inflammatory response at the tumor site by tumor-specific IgE may result in reduced tumor growth and tumor regression. Local mast cells may be activated to release TNF-alpha and other mediators that attract inflammatory cells, such as eosinophils and macrophages, to the tumor site. It may even be expected that eosinophils perform IgE-mediated lysis of tumor cells. The G250 IgE binds an antigen present on renal cell carcinoma. Mast cells were assayed for activation by G250 IgE in vitro in the presence of G250-positive tumor cells, by determination of the release of TNF-alpha and histamine. In parallel, G250 IgG1, IgG2a, and IgG2b, bound to tumor cells, were tested for their ability to activate mast cells. Tumor-specific IgE was capable of activating mast cells in the presence of tumor cells. This activation was specific and required the presence of the antigen on the tumor cell surface and recognition of the tumor cell by the IgE. G250 IgE mediated mast cell activation when present in the medium as well as being preloaded on either tumor cells or mast cells. Preincubation of mast cells with irrelevant IgE did not block specific G250 IgE-mediated mast cell activation. Upon activation, mast cells released histamine and TNF-alpha, as was detected in cytotoxicity assays with TNF-alpha-sensitive target cells (WEHI). G250 IgG2a also induced efficient mast cell activation, comparable to the effect of G250 IgE. Mast cells can be triggered to release mediators such as TNF-alpha by IgE in the presence of tumor cells expressing specific antigen. Whether mast cell activation contributes to antitumor effects observed during antibody-based immunotherapy of tumors deserves further investigation.
Luiten
R M
RM
Department of Pathology, State University of Leiden, The Netherlands.
Fleuren
G J
GJ
Warnaar
S O
SO
Litvinov
S V
SV
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology* / Q000494:pharmacology*; D007132:Immunoglobulin Isotypes / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000276:immunology*; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007132:Immunoglobulin Isotypes; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E