Sialyl-Tn vaccine induces antibody-mediated tumour protection in a relevant murine model.
Changes in the composition of glycans added to glycoproteins and glycolipids are characteristic of the change to malignancy. Sialyl-Tn (STn) is expressed by 25-30% of breast carcinomas but its expression on normal tissue is highly restricted. Sialyl-Tn is an O-linked disaccharide that can be carried on various glycoproteins. One such glycoprotein MUC1 is expressed by the vast majority of breast carcinomas. Both STn and MUC1 have been considered as targets for immunotherapy of breast cancer patients. Here we used different immunogens to target STn in an MUC1 transgenic mouse model of tumour challenge. We show that synthetic STn coupled to keyhole limpet haemocyanin (Theratope), induced antibodies to STn that recognised the glycan carried on a number of glycoproteins and in these mice a significant delay in tumour growth was observed. The protection was dependent on STn being expressed by the tumour and was antibody mediated. Affinity chromatography of the STn-expressing tumour cell line, followed by mass spectrometry, identified osteopontin as a novel STn-carrying glycoprotein which was highly expressed by the tumours. These results suggest that if antibodies can be induced to a number of targets expressed by the tumour cells, a humoral response can be effective in controlling tumour growth.
Julien
S
S
Breast Cancer Biology Group, King's College London, London SE1 9RT, UK.
Picco
G
G
Sewell
R
R
Vercoutter-Edouart
A-S
AS
Tarp
M
M
Miles
D
D
Clausen
H
H
Taylor-Papadimitriou
J
J
Burchell
J M
JM
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology* / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000276:immunology* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006433:Hemocyanins / Q000276:immunology; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D018396:Mucin-1 / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D014612:Vaccines / Q000276:immunology*
D000906:Antibodies; D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D018396:Mucin-1; D014612:Vaccines; C055491:sialosyl-Tn antigen; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin