title: Peptides mimicking GD2 ganglioside elicit cellular, humoral and tumor-protective immune responses in mice.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Assefa
authors.initials: A
authors.lastname: Wondimu
authors.forename: Tianqian
authors.initials: T
authors.lastname: Zhang
authors.forename: Thomas
authors.initials: T
authors.lastname: Kieber-Emmons
authors.forename: Phyllis
authors.initials: P
authors.lastname: Gimotty
authors.forename: Katrin
authors.initials: K
authors.lastname: Sproesser
authors.forename: Rajasekharan
authors.initials: R
authors.lastname: Somasundaram
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.forename: Chun-Yen
authors.initials: CY
authors.lastname: Tsao
authors.forename: Dorothee
authors.initials: D
authors.lastname: Herlyn
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000917:Antibody Formation; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D045744:Cell Line, Tumor; D005260:Female; D005732:Gangliosides / Q000276:immunology* / Q000378:metabolism; D007111:Immunity, Cellular; D016233:Immunotherapy, Active; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008545:Melanoma; D051379:Mice; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology; D011485:Protein Binding; D022223:Vaccines, Subunit / Q000276:immunology / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D005732:Gangliosides; D019151:Peptide Library; D010455:Peptides; D022223:Vaccines, Subunit; C019403:ganglioside, GD2