Anti-ganglioside anti-idiotypic vaccination: more than molecular mimicry

Ana M H Vázquez,Ana M V López,Nely Rodrèguez-Zhurbenko

doi:10.3389/fonc.2012.00170

Abstract

Surgery, chemotherapy, and radiation therapy are standard modalities for cancer treatment, but the effectiveness of these treatments has reached a plateau. Thus, other strategies are being explored to combine with the current treatment paradigms in order to reach better clinical results. One of these approaches is the active immunotherapy based on the induction of anti-tumor responses by anti-idiotypic vaccination. This approach arose from Jerne’s idiotypic network theory, which postulates that B lymphocytes forms a functional network, with a role in the establishment of the immune repertoires, in the regulation of natural antibody production and even in the establishment of natural tolerance. Due to the large potential diversity of the immunoglobulin variable regions, the idiotypes repertoire can mimic the universe of self and foreign epitopes, even those of non-protein nature, like gangliosides. Gangliosides are sialic acid-containing glycolipids that have been considered attractive targets for cancer immunotherapy, based on the qualitative and quantitative changes they suffer during malignant transformation and due to their importance for tumor biology. Although any idiotype could be able to mimic any antigen, only those related to antigens involved in functions relevant for organism homeostasis, and that in consequence has been fixed by evolution, would be able not only to mimic, but also to activate the idiotypic cascades related with the nominal antigen. The present review updates the results, failures and hopes, obtained with ganglioside mimicking anti-idiotypic antibodies and presents evidences of the existence of a natural response against gangliosides, suggesting that these glycolipids could be idiotypically relevant antigens.

Highlights

GANGLIOSIDES Gangliosides are glycosphingolipids present in the outer leaflet of the plasma membranes, where significantly contribute to the surface properties of cells (Sorice et al, 1997)
The metastatic capacity of the cells is strongly affected by the gangliosides expressed on the cell membranes: disialogangliosides GD2 and GD3 participate in the anchoring of the melanoma and neuroblastoma metastatic cells to the extracellular matrix proteins (Cheresh et al, 1986; Fredman et al, 2003)
Comparing the ganglioside pattern expressed by the primary tumor or the metastatic cells of a melanoma patient, gangliosides expression was higher in the last ones, especially GD1

Summary

Introduction

GANGLIOSIDES Gangliosides are glycosphingolipids present in the outer leaflet of the plasma membranes, where significantly contribute to the surface properties of cells (Sorice et al, 1997). Occurring antibodies reacting with tumor-associated gangliosides have been detected in cancer patients and in healthy donors. It has been reported the ability of a murine anti-GM2 to induce apoptosis through caspase activation in lymphoma, melanoma, and lung cancer cells expressing the antigen (Retter et al, 2005).

Results

Conclusion