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 Teo
  • Paul J. Utz
  • Joseph A. Mollick
Original article

Abstract

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.

Keywords

Tumor immunity Antibodies Mast cells Eosinophils 

Abbreviations

ADCC

Antibody-dependent cell-mediated cytotoxicity

ANOVA

Analysis of variance

CBEos

Cord blood-derived eosinophils

CBMC

Cord blood-derived mast cell

CFSE

Carboxyfluorescein diacetate succinimidyl ester

E:T

Effector to target ratio

FcεRI

Fragment crystallizable epsilon receptor I

hCD20

Human CD20

hMUC1

Human mucin 1

hSCF

Human stem cell factor

Ig

Immunoglobulin

IL

Interleukin

i.p.

Intraperitoneal

i.v.

Intravenous

mAb

Monoclonal antibody

MAHA

Mouse anti-human antibody

PBMC

Peripheral blood mononuclear cell

PI

Propidium iodide

SAM

Significance analysis of microarrays

s.c.

Subcutaneous

SCID

Severe combined immunodeficiency

SD

Standard deviation

TRAIL

TNF-related apoptosis inducing ligand

TNF

Tumor necrosis factor

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
  • 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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