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

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.

New perspectives on corpora amylacea in the human brain

“…Moreover, as the neo-epitopes that are target of natural IgMs have also been observed in PAS granules in mice 12 15 , these properties could perhaps be expanded to other PGBs, making it necessary to study the presence of neo-epitopes in other related brain degenerative bodies such as Lafora bodies from Lafora disease or Bielschowsky bodies from Bielschowsky body disease. In the same way in which the presence of neo-epitopes in certain malignant tumor cells and the presence of IgMs directed against these neo-epitopes is a recent field of study in the therapy and diagnosis of cancerous processes 25 41 42 , so the existence of neo-epitopes on CA and other degenerative brain structures and the presence of natural IgM antibodies directed against them could become a new focus of the study of age-related or pathological degenerative brain processes. It may open up new lines of research into PGBs and their physiopathological roles.…”

Natural Antibodies as Rheostats for Susceptibility to Chronic Diseases in the Aged

“…Somewhat akin to the correlative results noted above with respect to MGO-modified apoB100 peptide, patients with lung cancer lack or have very low levels of anti-NGcGM3 antibodies ( 41 ). Separately, an anti-idiotypic antibody vaccine (racotumomab) that displays the “internal image” of NGcGM3 has been developed to stimulate production of anti-NGcGM3 antibodies ( 69 – 71 ). In a recent clinical trial for maintenance treatment after first line chemotherapy in non-small cell lung cancer patients, racotumomab significantly prolonged overall survival and progression free survival, and those patients experiencing the greatest antibody response had the best outcomes ( 69 , 72 ).…”

Tumor-Associated Disialylated Glycosphingolipid Antigen-Revealing Antibodies Found in Melanoma Patients' Immunoglobulin Repertoire Suggest a Two-Direction Regulation Mechanism Between Immune B Cells and the Tumor

“…The potential use of anti-idiotypic antibodies for cancer treatment continues to be a challenge for tumor immunotherapy. Failures and hopes obtained, with ganglioside mimicking anti-idiotypic antibodies and the existence of a natural response against gangliosides, suggest that these glycolipids could be idiotypically relevant antigens (37, 38). Our present results help to better understand this essential field.…”