Cancer Immunology, Immunotherapy

, Volume 61, Issue 9, pp 1535–1546 | Cite as

Animal models for IgE-meditated cancer immunotherapy

  • Tracy R. Daniels
  • Otoniel Martínez-Maza
  • Manuel L. Penichet
Symposium-in-writing paper

Abstract

Although most monoclonal antibodies developed for cancer therapy are of the IgG class, antibodies of the IgE class have certain properties that make them attractive as cancer therapeutics. These properties include the superior affinity for the Fc epsilon receptors (FcεRs), the low serum level of IgE that minimizes competition of endogenous IgE for FcεR occupancy, and the ability to induce a broad and vigorous immune response through the interaction with multiple cells including mast cells, basophils, monocytes, macrophages, dendritic cells, and eosinophils. Tumor-targeted IgE antibodies are expected to harness the allergic response against tumors and activate a secondary, T-cell-mediated immune response. Importantly, the IgE antibody can be used for passive immunotherapy and as an adjuvant of cancer vaccines. However, there are important limitations in the use of animal models including the fact that human IgE does not interact with rodent FcεRs and that there is a different cellular distribution of FcεRs in humans and rodents. Despite these limitations, different murine models have been used with success to evaluate the in vivo anti-cancer activity of several IgE antibodies. These models include wild-type immunocompetent animals bearing syngeneic tumors, xenograft models using immunocompromised mice bearing human tumors and reconstituted with human effector cells, and human FcεRIα transgenic mice bearing syngeneic tumors. In addition, non-human primates such as cynomolgus monkeys can be potentially used for toxicological and pharmacokinetic studies. This article describes the advantages and disadvantages of these models and their use in evaluating the in vivo properties of IgE antibodies for cancer therapy.

Keywords

IgE Animal models Cancer AllergoOncology Immunotherapy 

Notes

Acknowledgments

Our work has been supported in part by the NIH/NCI grants K01CA138559, R41CA137881, R01CA1368413, K01CA138559, R01CA57152, R01CA121195, the Susan G. Komen Breast Cancer Foundation Basic, Clinical and Translational Research Grant BCTR0706771, and the NIH Fogarty AITRP-AIDS Malignancies Program D43TW000013-S1.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Tracy R. Daniels
    • 1
  • Otoniel Martínez-Maza
    • 2
    • 3
    • 4
    • 5
  • Manuel L. Penichet
    • 1
    • 2
    • 3
    • 6
  1. 1.Division of Surgical Oncology, Department of Surgery, David Geffen School of MedicineUniversity of California, Los AngelesLos AngelesUSA
  2. 2.Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of MedicineUniversity of California, Los AngelesLos AngelesUSA
  3. 3.Jonsson Comprehensive Cancer CenterUniversity of California, Los AngelesLos AngelesUSA
  4. 4.Department of Obstetrics and Gynecology, David Geffen School of MedicineUniversity of California, Los AngelesLos AngelesUSA
  5. 5.Department of Epidemiology, School of Public HealthUniversity of California, Los AngelesLos AngelesUSA
  6. 6.The Molecular Biology InstituteUniversity of California, Los AngelesLos AngelesUSA

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