Priming characteristics of peptide mimotopes of carbohydrate antigens

Monzavi‐Karbassi, Behjatolah; Shamloo, Shahram; Kieber‐Emmons, Matthew T.; Jousheghany, Fariba; Luo, Ping; Lin, Kaity; Cunto-Amesty, Gina; Weiner, David B.; Kieber‐Emmons, Thomas

doi:10.1016/s0264-410x(02)00703-x

Cited by 40 publications

(26 citation statements)

References 31 publications

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“…Furthermore, the generated immune responses could be further manipulated with various delivery schedules, i.e. 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).…”

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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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%

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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“…Mimotopes function as xenoantigens and, consequently, can overcome tolerance to carbohydrate self-antigens. Unlike carbohydrate antigens and carbohydrate-conjugate vaccines, we have shown that mimotopes prime B-and T-cells for subsequent memory of carbohydrate antigens, facilitating long-term surveillance through recall of carbohydrate immune responses (23). This effect is a major advantage that would minimize the need for constant boosting.…”

Section: Introductionmentioning

confidence: 99%

Evaluating strategies to enhance the anti-tumor immune response to a carbohydrate mimetic peptide vaccine

Monzavi‐Karbassi

Pashov²,

Jousheghany³

et al. 2006

Int J Mol Med

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Abstract. Carbohydrate mimetic peptides of tumor associated carbohydrate antigens (TACA) are T-cell-dependent antigens and, therefore, immunization with these surrogates is predicted to overcome the low immunogenicity of carbohydrate antigens. Consistent with this hypothesis, we show that among the potential immune cells involved, peptide immunization led to an increase in T-cell populations. While peptide mimetics may also function as TLR binding ligands, we did not observe evidence of involvement of NK cells. Examining tumor challenged animals, we observed that peptide immunization and not tumor cells rendered IL-12 responsiveness to T-cells, as T-cells from peptide-immunized mice produced IFN-Á upon stimulation with IL-12. Cyclophosphamide administration enhanced the anti-tumor efficacy of the vaccine, which was achieved by enhancing T-cell responses with no effect on NK cell population. Prophylactic immunization of mice with a DNA construct encoding carbohydrate mimetic peptides indicated a specific role for the mimotope vaccine in antitumor immune responses. These data suggest a role for both CD4 + and CD8 + T-cells induced by mimotopes of TACA in protective immunity against tumor cells.

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“…Toward this end, we have shown that peptide mimotopes can induce humoral responses that mediate tumor-specific complement-dependent cytotoxicity (CDC) 3 (5,6) and tumorspecific cellular responses (7). We have also shown that priming with peptide mimotopes followed by boosting with carbohydrate Ag can prolong the IgM response in mice, a benefit that is perceived to be of value for cancer vaccines in humans (8). Because it is expected that complement inhibitors expressed on a tumor cell surface can impair CDC, we have turned our attention to a strategy of developing mimotopes that will induce Abs that trigger apoptotic mechanisms.…”

mentioning

confidence: 99%

Reduction of Spontaneous Metastases through Induction of Carbohydrate Cross-Reactive Apoptotic Antibodies

Monzavi‐Karbassi

Artaud

Jousheghany

et al. 2005

The Journal of Immunology

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The selective targeting of tumor-associated carbohydrate Ags by the induction of serum Abs that trigger apoptosis of tumor cells as a means to reduce circulating tumor cells and micrometastases would be an advantage in cancer vaccine development. Some plant lectins like Griffonia simplicifolia lectin I and wheat germ agglutinin mediate the apoptosis of tumor cells. We investigated the possibility of using these lectins as templates to select peptide mimotopes of tumor-associated carbohydrate Ags as immunogens to generate cross-reactive Abs capable of mediating apoptosis of tumor cells. In this study, we show that immunization with a mimotope selected based on its reactivity with Griffonia simplicifolia lectin I and wheat germ agglutinin induced serum IgM Abs in mice that mediated the apoptosis of murine 4T1 and human MCF7 cell lines in vitro, paralleling the apoptotic activity of the lectins. Vaccine-induced anti-carbohydrate Abs reduced the outgrowth of micrometastases in the 4T1 spontaneous tumor model, significantly increasing survival time of tumor-bearing animals. This finding parallels suggestions that carbohydrate-reactive IgM with apoptotic activity may have merit in the adjuvant setting if the right carbohydrate-associated targets are identified.

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Priming characteristics of peptide mimotopes of carbohydrate antigens

Cited by 40 publications

References 31 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

Evaluating strategies to enhance the anti-tumor immune response to a carbohydrate mimetic peptide vaccine

Reduction of Spontaneous Metastases through Induction of Carbohydrate Cross-Reactive Apoptotic Antibodies

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