DNA Vaccine Expressing the Mimotope of GD2 Ganglioside Induces Protective GD2 Cross-reactive Antibody Responses

Bolesta, Elizabeth; Kowalczyk, Aleksandra; Wierzbicki, Andrzej; Rotkiewicz, Piotr; Bambach, Barbara; Tsao, Chun-Yen; Horwacik, Irena; Koliński, Andrzej; Rokita, Hanna; Brecher, Martin L.; Wang, Xinhui; Ferrone, Soldano; Kozbor, Danuta

doi:10.1158/0008-5472.can-04-2164

Cited by 63 publications

(56 citation statements)

References 43 publications

(39 reference statements)

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“…In comparison, our 5 peptides are of different length, have no considerable sequence identity, and have no obvious similarities in motif. Linear 15 aa peptides were isolated with 14G2a mAb (29). Forster-Waldl and coresearchers reported phage clones expressing cyclic peptides build by 10 amino acids, which were looped by the addition of 2 flanking cysteine residues, and were isolated from the phage-displayed library based on pIII fusions, and with the anti-GD2 ganglioside antibody ch14.18.…”

Section: Discussionmentioning

confidence: 99%

“…prime/boost strategies with peptides and carbohydrate, or a DNA vaccination approach (21,40). The presence of anti-GD2 ganglioside responses has already been investigated with application of mimicking peptides (29,41). Indeed, mutual relationships between the observed mimicry in binding to 14G2a mAb and the functional ability to induce GD2 ganglioside-specific immune responses must be established if the GD2 mimicking peptides isolated from the LX-8 library are to be evaluated as components of anti-tumor vaccines.…”

Section: Discussionmentioning

confidence: 99%

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Selection of novel peptide mimics of the GD2 ganglioside from a constrained phage-displayed peptide library

Horwacik

Czaplicki²,

Talarek³

et al. 2007

Int J Mol Med

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Abstract. Aberrant glycosylation is a universal feature of cancer cells. There are quantitative and qualitative changes in expression of gangliosides observed in tumors of a neuroectodermal origin such as neuroblastoma, melanoma and astrocytoma. The presence of large amounts of GD2 ganglioside on neuroblastoma cells, as compared to normal cells, opens the possibilities to use the tumor-associated carbohydrate antigen in diagnosis and immunotherapeutic approaches. In the quest for immunogens potentially capable of eliciting anti-GD2 ganglioside immune responses, we performed affinity purification of phage-displayed peptides from the LX-8 library (12-mer containing disulphide bridge). The library was screened with the biotinylated anti-GD2 ganglioside 14G2a mAb monoclonal antibody. Our goal was to isolate and characterize peptide mimics of GD2 ganglioside. Numerous individual phage clones that bound 14G2a mAb were identified with the application of immunoblotting technique in the phage pools yielded from the pannings. The phage-borne peptides were tested for their anti-GD2 ganglioside antibody binding ability using ELISA. Among these clones five different phage-displayed peptide sequences were identified. Moreover, we showed that the secondary structure of the peptides, stabilized by the disulfide bridging between cysteine residues at positions 2 and 11, was crucial for the binding of the peptides to 14G2a mAb. In a separate set of experiments, we observed a competition of the peptides, expressed on phages as well as in their synthetic form, with the nominal antigen GD2 ganglioside expressed on IMR-32 neuroblastoma cells for binding to 14G2a mAb. Based on the obtained results we concluded that all of these 5 peptides were mimics of the GD2 ganglioside.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Selection of novel peptide mimics of the GD2 ganglioside from a constrained phage-displayed peptide library

Horwacik

Czaplicki²,

Talarek³

et al. 2007

Int J Mol Med

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“…These were, to the best of our knowledge, the first peptide mimics generated for this ganglioside antigen. Early last year, another group described the definition of a GD2 mimotope [45], which they encoded in a minigene for a DNA vaccination approach. In the present study, we aimed to assess whether 'our' cyclic mimotopes were immunogenic and whether the induced antibodies recognize the original antigen GD2.…”

Section: Discussionmentioning

confidence: 99%

Induction of IgG antibodies against the GD2 carbohydrate tumor antigen by vaccination with peptide mimotopes

et al. 2006

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The disialoganglioside GD2, a carbohydrate antigen, is expressed on all tumors of neuroectodermal origin, including melanoma, neuroblastoma, sarcoma and small cell lung cancer. Due to its specific expression on tumor surfaces, GD2 is an attractive target for immunotherapies. The mouse/human chimeric anti-GD2 mAb ch14.18 is already applied in melanoma and neuroblastoma trials as a passive immunotherapy. To establish an active immunotherapy alternative, we aimed to replace the poorly immunogenic ganglioside with immunogenic peptides. Previously, we used the ch14.18 antibody to select GD2 peptide mimics from a phage display library. In the present study, two mimics of the ch14.18 epitope were coupled to keyhole limpet hemocyanin and used for immunizing BALB/c mice. Induction of a specific humoral immune response towards the original antigen GD2, both purified and expressed on neuroblastoma and melanoma cells, could be demonstrated in ELISA, Western blot, and immunofluorohistochemistry. As the elicited antibodies were of the IgG isotype, the mimotope conjugates were capable of recruiting T cell help and inducing memory phenomena. In conclusion, we show that an epitope of the carbohydrate antigen GD2 can successfully be translated into immunogenic peptide mimotopes. Our immunization experiments indicate that GD2 mimotopes are suitable for active immunotherapy of GD2-expressing tumors.

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“…Mimotope vaccines have been applied naked [66], or using Salmonella as a 'Trojan horse' for oral vaccine formulation [67,73]. Generally, prime-boost regimens or multi-epitope vaccines induced higher affinities and functional antitumor effects [69,81,82]; molecular modeling and mutagenesis studies [84] or docking experiments [73] may also help to select and improve the potential of a mimotope.…”

Section: The Principle Of Mimotope Vaccinesmentioning

confidence: 99%

Cancer vaccines inducing antibody production: more pros than cons

Jensen‐Jarolim¹,

Singer²

2011

Expert Review of Vaccines

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DNA Vaccine Expressing the Mimotope of GD2 Ganglioside Induces Protective GD2 Cross-reactive Antibody Responses

Cited by 63 publications

References 43 publications

Selection of novel peptide mimics of the GD2 ganglioside from a constrained phage-displayed peptide library

Selection of novel peptide mimics of the GD2 ganglioside from a constrained phage-displayed peptide library

Induction of IgG antibodies against the GD2 carbohydrate tumor antigen by vaccination with peptide mimotopes

Cancer vaccines inducing antibody production: more pros than cons

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