Abstract
Described in several epithelial cancer cells, Tn- (GalNAcα1-O-Ser/Thr) and T- (Galβ3GalNAcα1-O-Ser/Thr) antigens are examples of tumor-associated antigens. Increased expression of Tn- and T-antigens is associated with tumor invasion and metastasis, and patients with high concentration of anti-Tn and anti-T antibodies have a more benign evolution of pathology. Asialofetuin (ASF) and ovine submaxillary mucin (OSM) are two glycoproteins that expose T- and Tn-antigen, respectively. In this work, using ASF or OSM we affinity-purified anti-T and anti-Tn antibodies from normal human plasma and tested their ability to specifically recognize tumor human tissues. Whereas purified anti-T antibodies (purity degree increase of 127-fold, and 22% recovery) were mainly IgG, for purified anti-Tn antibodies (purity degree enhancement of 125-fold, and 26% yield) the IgM fraction was predominant over the IgG one. IgG2 subclass was significantly enriched in both purified antibody samples. Purified antibodies did not bind normal human tissue (0/42), although recognized malignant tissues from different origin such as colon carcinoma (11/77 by anti-Tn; 7/79 by anti-T), breast carcinoma (10/23 by anti-Tn; 7/23 by anti-T), and kidney carcinoma (45/51 by anti-Tn; 42/51 by anti-T). Our results suggest that purified human anti-Tn and anti-T antibodies have a potential as anti-tumor therapeutic agents; restoring their levels in human sera could positively affect the evolution of patients with epithelial tumor pathologies.
Highlights
The phenotype of epithelial cancer cell is greatly conditioned by glycoconjugates from glycoproteins, glycolipids and glycosaminoglycans
Pathology evolution of patients with high concentration of anti-Tn and anti-T antibodies is more benign[11]. These results suggest that restitution of human anti-Tn and anti-T antibodies should positively affect the evolution of patients with epithelial tumor pathologies
The purity of eluted proteins was evaluated by SDS-PAGE stained with Coomassie Brilliant Blue (CBB), and immunoglobulin isotypes were identified by western blot (WB) using anti-human IgG, IgM and total immunoglobulin antibodies (Fig. 1)
Summary
The phenotype of epithelial cancer cell is greatly conditioned by glycoconjugates from glycoproteins, glycolipids and glycosaminoglycans. O-GalNAc glycans present on carcinoma cells are commonly truncated structures exposing cryptic regions that are normally hidden. Tumor associated-antigens (TAAs) are terminal residues chemically well know with more often in cancer cells than normal cells. Normal human sera contain multiple antibodies recognizing specific glycan residues[7], and different hypothesis attempt to explain the origin of natural anti-glycan antibodies[8]. Natural anti-Tn and anti-T antibodies are present in normal human sera[9], and studies of anti-Tn and anti-T antibodies in patients with epithelial carcinomas showed reduced levels of these anti-glycan antibodies[10]. In the present study we purified two populations of antibodies (anti-Tn and anti-T) from pooled human plasma and evaluated their ability to recognize human carcinoma tissue, aiming to uncover potential applications in antineoplastic therapy
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