Using the allergic immune system to target cancer: activity of IgE antibodies specific for human CD20 and MUC1.
Monoclonal antibodies are widely used in the treatment of many B cell lymphomas and certain solid tumors. All currently approved therapeutic monoclonal antibodies are of the immunoglobulin G (IgG) isotype. We hypothesized that tumor-specific monoclonal antibodies of the IgE isotype may serve as effective cancer therapeutics. To test this hypothesis, we produced mouse-human chimeric IgE antibodies specific for the human B cell antigen CD20 and the epithelial antigen MUC1. We demonstrate here that anti-hCD20 IgE antibodies have in vitro cytotoxic activity when used with purified allergic effector cells derived from umbilical cord blood. At an effector-tumor ratio of 2:1, mast cells and tumor-specific IgE induced a 2.5-fold increase in tumor cell death, as compared to control IgE. Similar results were observed when eosinophils were used as effector cells. In an in vivo murine model of breast carcinoma, administration of anti-hMUC1 IgE reduced the growth of MUC1(+) tumors by 25-30 % in hFcεRI transgenic mice. In contrast, local production of IgE and cytokines chemotactic for macrophages, eosinophils and mast cells led to complete tumor eradication. These results suggest that allergic effector cells activated by IgE and cell surface antigens have the capacity to induce tumor cell death in vitro and in vivo. The use of chimeric antibodies and hFcεRI transgenic mice will greatly enhance investigations in the nascent field of allergo-oncology.
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. pearline@stanfordalumni.org
Pearline Zhaoying
PZ
Teo
Paul J
PJ
Utz
Joseph A
JA
Mollick
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D018951:Antigens, CD20 / Q000276:immunology* / Q000378:metabolism; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism; D016466:CHO Cells; D002277:Carcinoma / Q000276:immunology / Q000378:metabolism; D016923:Cell Death / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D006224:Cricetinae; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000276:immunology / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D000954:Antigens, Surface; D018925:Chemokines; C060192:MUC1 protein, human; D018396:Mucin-1; D007073:Immunoglobulin E