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Peptides mimicking GD2 ganglioside elicit cellular, humoral and tumor-protective immune responses in mice

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Abstract

Introduction

Because of its restricted distribution in normal tissues and its high expression on tumors of neuroectodermal origin, GD2 ganglioside is an excellent target for active specific immunotherapy. However, GD2 usually elicits low-titered IgM and no IgG or cellular immune responses, limiting its usefulness as a vaccine for cancer patients. We have previously shown that anti-idiotypic monoclonal antibody mimics of GD2 can induce antigen-specific humoral and cellular immunity in mice, but inhibition of tumor growth by the mimics could not be detected.

Methods and results

Here, we isolated two peptides from phage display peptide libraries by panning with GD2-specific mAb ME361. The peptides inhibited binding of the mAb to GD2. When coupled to keyhole limpet hemocyanin (KLH) or presented as multiantigenic peptides in QS21 adjuvant, the peptides induced in mice antibodies binding specifically to GD2 and delayed-type hypersensitive lymphocytes reactive specifically with GD2-positive D142.34 mouse melanoma cells. Induction of delayed-type hypersensitivity (DTH) reaction was dependent on CD4-positive lymphocytes. The immunity elicited by the peptides significantly inhibited growth of GD2-positive melanoma cells in mice.

Conclusion

Our study suggests that immunization with peptides mimicking GD2 ganglioside inhibits tumor growth through antibody and/or CD4-positive T cell-mediated mechanisms. Cytolytic T lymphocytes most likely do not play a role. Our results provide the basis for structural analysis of carbohydrate mimicry by peptides.

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Abbreviations

Ab2:

Anti-idiotypic antibody

DTH:

Delayed-type hypersensitivity

KLH:

Keyhole limpet hemocyanin

MAP:

Multiple-antigen peptides

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Acknowledgments

We thank Koichi Furukawa, Nagasaki University, Nagasaki, Japan, for providing D142.34 mouse melanoma cells. This work was supported by grants CA25874, CA93372, CA89480 and CA10815 from the National Institutes of Health and by the Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health.

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Authors and Affiliations

  1. Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA

    Assefa Wondimu, Tianqian Zhang, Katrin Sproesser, Rajasekharan Somasundaram & Dorothee Herlyn

  2. Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA

    Thomas Kieber-Emmons

  3. Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Phyllis Gimotty

  4. Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA

    Soldano Ferrone & Chun-Yen Tsao

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  1. Assefa Wondimu
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  2. Tianqian Zhang
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Correspondence to Dorothee Herlyn.

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A. Wondimu and T. Zhang contributed equally to this work.

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Wondimu, A., Zhang, T., Kieber-Emmons, T. et al. Peptides mimicking GD2 ganglioside elicit cellular, humoral and tumor-protective immune responses in mice. Cancer Immunol Immunother 57, 1079–1089 (2008). https://doi.org/10.1007/s00262-007-0439-4

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  • DOI: https://doi.org/10.1007/s00262-007-0439-4

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