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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.
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1 Universidad Nacional de Córdoba, Ciudad Universitaria, Centro de Investigaciones en Química Biológica de Córdoba, CIQUIBIC, CONICET and Departamento de Química Biológica Ranwel Caputto, Facultad de Ciencias Químicas, Córdoba, Argentina (GRID:grid.10692.3c) (ISNI:0000 0001 0115 2557); Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Centro de Microscopía Electrónica, Bv. De la Reforma y Enfermera Gordillo, Ciudad Universitaria, Córdoba, Argentina (GRID:grid.10692.3c) (ISNI:0000 0001 0115 2557)
2 Laboratorio de Alta Complejidad, Fundacion para el Progreso de la Medicina, Córdoba, Argentina (GRID:grid.10692.3c)
3 Universidad Nacional de Córdoba, Ciudad Universitaria, Centro de Investigaciones en Química Biológica de Córdoba, CIQUIBIC, CONICET and Departamento de Química Biológica Ranwel Caputto, Facultad de Ciencias Químicas, Córdoba, Argentina (GRID:grid.10692.3c) (ISNI:0000 0001 0115 2557)