Purified human anti-Tn and anti-T antibodies specifically recognize carcinoma tissues

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.

Fusobacterium nucleatum and cancer

“…In normal cells, N‐acetylneuraminic acid, the predominant sialic acid in human and many mammalian cells, is frequently added to cap and mask the GalNAc and Gal‐GalNAc residues 96,97 . However, in many carcinomas (such as CRC), truncated O‐GalNAc glycans are formed, and sialic acid is not added to the exposed GalNAc and Gal‐GalNAc 97,98 . As a result, high levels of GalNAc (Tn antigen) and Gal‐GalNAc (T antigen) have been detected in colon cancer and additional human tumors including lung, breast and liver carcinoma 96,99,100 .…”

Pathogenesis of IgA Nephropathy: Current Understanding and Implications for Development of Disease-Specific Treatment

“…In fact, human anti-Tn antibodies, including IgG and IgM isotypes, affinity-purified using terminal GalNAcα-containing matrix, demonstrate higher affinity for other glycan structures compared to terminal GalNAcα, including bacteria-derived products and cell-wall structures [ 128 ]. At least some of these antibodies clearly recognize tumor-associated Tn antigens [ 129 ]. MUC1 is a glycoprotein constitutively expressed by epithelial cells in many organs, including the lungs and gastrointestinal tract.…”

How glycobiology can help us treat and beat the COVID-19 pandemic

“…These O-GalNAc residues were described in N-terminal domain peptide 28 YTNSFTR 34 , T323 (RBD hinge) and T678 in the S1 subunit and S686 in S2 subunit of SARS-CoV-2 spike glycoproteins ( 26 ). Tn, T, and sialyl T antigens are cryptic human residues in healthy people, and these anti-O-GalNAc glycan antibodies are commonly present in normal human sera where they can be purified from ( 67 ). The use of human anti-Tn, -T and -sialyl T antibodies is an original approach that should also be considered as passive immunotherapy for COVID-19 disease ( Table 1 ).…”

“…The use of human anti-Tn, -T and -sialyl T antibodies is an original approach that should also be considered as passive immunotherapy for COVID-19 disease ( Table 1 ). These natural anti-glycan antibodies are relevant components of innate immunity against cancer cells, where IgM isotype has predominant participation ( 67 ). Co-morbidity of cancer disease and SARS-CoV-2 infection is often a cause of dead ( 5 ).…”