Cancer Immunology, Immunotherapy

, Volume 61, Issue 12, pp 2295–2309 | Cite as

Using the allergic immune system to target cancer: activity of IgE antibodies specific for human CD20 and MUC1

  • Pearline Zhaoying TeoEmail author
  • Paul J. Utz
  • Joseph A. Mollick
Original article


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.


Tumor immunity Antibodies Mast cells Eosinophils 



Antibody-dependent cell-mediated cytotoxicity


Analysis of variance


Cord blood-derived eosinophils


Cord blood-derived mast cell


Carboxyfluorescein diacetate succinimidyl ester


Effector to target ratio


Fragment crystallizable epsilon receptor I


Human CD20


Human mucin 1


Human stem cell factor










Monoclonal antibody


Mouse anti-human antibody


Peripheral blood mononuclear cell


Propidium iodide


Significance analysis of microarrays




Severe combined immunodeficiency


Standard deviation


TNF-related apoptosis inducing ligand


Tumor necrosis factor



We thank J.P. Kinet from Harvard for the hFcεRI transgenic mice; H. Kita from the Mayo Clinic for helpful advice on eosinophils; O. Finn from the University of Pittsburgh for the VU-3C6 and VU-4H5 hybridomas; R. Levy from Stanford for the OCI-Ly8 lymphoma line; and Amgen, Inc. for rhSCF and rhIL6. We also thank A. Piliponsky and E. Rios from the laboratory of Stephen Galli and Y. Rosenberg-Hassan from the Stanford Human Immune Monitoring Core for helpful discussion and technical assistance; and R. Levy, S. Galli, E. Engleman and members of the Utz lab for critical review of this manuscript. P.T. was funded by the Agency for Science, Technology and Research (A*STAR) Singapore. J.M. was funded by NIH Grant CA111639-01A1 (NCI) and also supported by a generous gift from Margaret and Richard Yen. P.J.U. was the recipient of a Donald E. and Delia B. Baxter Foundation Career Development Award and was supported by the Dana Foundation, the Floren Family Trust, the Ben May Trust, NIH Grants DK61934, AI50854, AI50865, AR49328, and NHLBI Proteomics Contract HHSN288201000034C.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

262_2012_1299_MOESM1_ESM.doc (3.7 mb)
Supplementary material 1 (DOC 3772 kb)


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Pearline Zhaoying Teo
    • 1
    • 3
    Email author
  • Paul J. Utz
    • 1
  • Joseph A. Mollick
    • 1
    • 2
  1. 1.Division of Immunology and Rheumatology, Department of MedicineStanford University School of MedicineStanfordUSA
  2. 2.Division of OncologyStanford Cancer Institute, Stanford University School of MedicineStanfordUSA
  3. 3.Molecular Engineering LabScience and Engineering Institutes, Agency for Science, Technology and ResearchSingaporeSingapore

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