Cancer Immunology, Immunotherapy

, Volume 57, Issue 7, pp 1079–1089 | Cite as

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

  • Assefa Wondimu
  • Tianqian Zhang
  • Thomas Kieber-Emmons
  • Phyllis Gimotty
  • Katrin Sproesser
  • Rajasekharan Somasundaram
  • Soldano Ferrone
  • Chun-Yen Tsao
  • Dorothee Herlyn
Original Article

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.

Keywords

GD2 Peptide mimics Antibodies DTH Tumor growth inhibition 

Abbreviations

Ab2

Anti-idiotypic antibody

DTH

Delayed-type hypersensitivity

KLH

Keyhole limpet hemocyanin

MAP

Multiple-antigen peptides

Notes

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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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Assefa Wondimu
    • 1
  • Tianqian Zhang
    • 1
  • Thomas Kieber-Emmons
    • 2
  • Phyllis Gimotty
    • 3
  • Katrin Sproesser
    • 1
  • Rajasekharan Somasundaram
    • 1
  • Soldano Ferrone
    • 4
  • Chun-Yen Tsao
    • 4
  • Dorothee Herlyn
    • 1
  1. 1.Wistar InstitutePhiladelphiaUSA
  2. 2.Department of PathologyUniversity of Arkansas for Medical SciencesLittle RockUSA
  3. 3.Department of Biostatistics and EpidemiologyUniversity of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of ImmunologyRoswell Park Cancer InstituteBuffaloUSA

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