Anti‐idiotypic antibody mimicking a T‐antigen‐specific lectin inhibits human epithelial tumor cell proliferation

Abstract

Cancer-associated mucins show frequent alterations of oligosaccharide chain profile. Terminal structures may be deleted, thereby exposing normally 'cryptic' structures such as Tn (GalNAcα-O-Ser/Thr) and T antigen (Galβ1-3GalNAcα-O-Ser/Thr). Overexpression of these commonly hidden glycoforms, and reduced level of naturally occurring anti-T or anti-Tn antibodies, is associated with epithelial tumor progression and aggressiveness. The lectin from the common edible mushroom Agaricus bisporus (ABL) shows high affinity binding to T antigen, and reversible noncytotoxic inhibitory effect on epithelial tumor cell proliferation. The aim of this study was to induce immune response with tumor-associated glycan specificity and biological activity similar to those of ABL. An anti-idiotypic (Id) antibody strategy was developed using ABL as first template. ABL was purified by affinity chromatography and assayed as immunogen in rabbit. Rabbit IgG was purified from anti-ABL serum using a protein G column, and specific anti-ABL IgG was obtained by affinity chromatography using immobilized ABL. Affinity-purified anti-ABL IgG contained an antibody fraction that recognizes the carbohydrate-binding site of ABL. This IgG was used as immunogen in mouse to yield anti-Id antibody recognizing tumor-associated glycans such as Tn and T antigen. Competitive assays showed that α-anomeric GalNAc is the main binding subsite of anti-Id antibody in glycan recognition. Anti-Id antibody bound human epithelial tumor cells, as shown by cell enzyme-linked immunosorbent assay and immunofluorescence. Anti-Id antibody raised by immunization with affinity-purified anti-ABL IgG had antiproliferative effect on human epithelial tumor cells through apoptosis induction similar to that of ABL. The anti-Id immune response developed here has potential application in cancer therapy.

Synthesis and cell-selective antitumor properties of amino acid conjugated tumor-associated carbohydrate antigen-coated gold nanoparticles

“…54 TF ag is an excellent target of anticancer therapeutic intervention, as it acts as a tumor antigen as well as a mediator of metastasis (via lectin-mediated adhesive events) in several solid tumor types. 55–58 Hence, a plethora of approaches have been explored to exploit TF ag as a target for both active 4,5,8 and passive 59–61 immunotherapy; in addition to strategies that inhibit cell adhesion. 57,58,62,63 It is now well established that TF ag engages a specific galectin, Galectin-3 (Gal-3), during the metastatic spread of certain TF ag -bearing tumors, and that this interaction can dictate the aggressiveness of the tumor.…”

The effects of dietary supplementation with Agaricales mushrooms and other medicinal fungi on breast cancer: Evidence-based medicine

“…In addition, lectins modify the cell cycle by inducing cell cycle arrest at the G2/M phase, promoting apoptosis, and stimulating non-apoptotic G1-phase accumulation mechanisms. Finally, lectins can also down-regulate telomerase activity and inhibit angiogenesis 16-20. …”

Iterative One‐Pot α‐Glycosylation Strategy: Application to Oligosaccharide Synthesis

“…This disaccharide conjugate is known as T antigen and is found to be over-expressed in mucosal cells under tumorigenic conditions. [39,40] The chief obstacle of the one-pot synthesis of 19 is the construction of the cis a-glycosidic bond. A one-pot synthesis of the protected core 1 serine has been previously reported by Takahashi, but the stereocontrol achieved was moderate.…”