A Mimic of Tumor Rejection Antigen-Associated Carbohydrates Mediates an Antitumor Cellular Response

The Journal of Immunology

Artaud

Jousheghany

et al. 2005

Self Cite

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.

Section: Discussionmentioning

confidence: 99%

Section: Flow Cytometrymentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

The Journal of Immunology

Artaud

Jousheghany

et al. 2005

Self Cite

“…We have shown that peptide 106 elicits anti-tumor CTLs that, in the presence of IL-12, lead to a complete eradication of tumors (30,32). To further explore the effect of mimotope immunization on the immune cell population and homeostasis in tumor-bearing mice, we analyzed the percentage of T-cells and NK cells in splenocytes collected from non-treated tumor-bearing mice and mice cured of their tumors after immunization.…”

Section: Mimotope Immunization Led To An Increase In T-cell Populatiomentioning

confidence: 99%

“…Secretion of suppressive cytokines, contact inhibition of CTL by tumor cells and the action of T regulatory cells (Tregs), NK and macrophages have been discussed as possible mechanisms of this immune dysfunction (25,(27)(28)(29). We have shown that therapeutic effectiveness of a mimotope-based vaccine depends on the tumor stage and time of vaccination (30). We speculated that suppression of the immune system and larger tumor size at the later stages are main causes of the failure of late vaccine administration.…”

Section: Introductionmentioning

confidence: 99%

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

Pashov²,

Jousheghany³

et al. 2006

Int J Mol Med

Self Cite

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.

Antigens: CarbohydratesII

Kieber-Emmons

Encyclopedia of Life Sciences

Kieber‐Emmons

2020

Glycosylation is critical for a wide range of biological processes across both normal and disease states. Carbohydrate antigens, for example, are polymeric chains of diverse monomeric sugar molecules that play a fundamental role in the pathogenicity and virulence of many organisms. Moreover, these pathogen‐associated glycan structures can also be found in association with other types of cells, including tumours. These types of glycan commonalities have helped generate critical discoveries in terms of glycan structure, allowing for the development of working hypotheses for their functions, in addition to the development of agents that target or mediate their expression levels. Therefore, through discussion of glycans as antigens, new insights of key molecular and cellular interactions between them and immune cells can be discerned, and the implication of these interactions in health and disease is enhanced. Numerous reviews and even this ELS series have described the structure of carbohydrates and glycans in general. Key Concepts Glycosylation is the most abundant post‐translational modification of proteins. Glycans expand the chemical diversity of the genetic code. Antigens are a collection of epitopes that affects recognition by the immune system. Antigens and immunogens are very different. Molecular mimicry of glycans profoundly affects the pathophysiology of infection and neoplasia. Lectin‐family receptors and antibodies have been used to define carbohydrate antigens. Clustering of epitopes defines glycan antigens better than nonclustered epitopes. Carbohydrate antigens can define danger signals to the immune system through pattern recognition receptors. Clustering associates with different B‐cell populations for processing as immunogens. MHC and T‐cell receptors see atoms in particular arrays, not as a single molecular species – hence cross‐reactivity with zwitterionic carbohydrate structures. While carbohydrate‐based vaccines have been developed, as cancer vaccines they are not as effective. Metabolism is the next frontier to understanding glycan expression patterns.