Expression profile of saccharide epitope CaMBr1 in normal and neoplastic tissue from dogs, cats, and rats: implication for the development of human-derived cancer vaccines.
CaMBr1 is a blood group-related tumour-associated antigen, whose pattern of expression provides a therapeutic window for passive or active immunotherapy and points to the promise of a vaccine against carcinomas overexpressing this antigen. In this context, an animal model that closely mimics the human situation would be extremely useful. We, therefore, utilised the murine monoclonal antibody MBr1, which defines CaMBr1, as a useful probe to detect the molecule targeted for vaccine development on canine and feline spontaneous breast and uterus tumours and on their normal counterparts, and on rat normal tissues and carcinoma cell lines. Immunoperoxidase staining of cryostat sections revealed homogeneous CaMBr1 expression only in normal feline uterus and a uterus papilloma, whereas MBr1 reactivity was very weak and heterogeneous in normal (1/3 and 1/3) and tumour (1/10 and 1/6) breast tissues from dogs and cats, respectively. In contrast, the data obtained in rat tissues were reproducible in the strains tested and showed that CaMBr1 was expressed in all epithelial tissues of the digestive tract, although with variable intensities. Monoclonal antibody staining appeared to correspond to membrane-bound structures as well as mucinous secretions. Similarly, secretion products of lactating mammary glands expressed CaMBr1. The spectrum of expression on rat digestive tract was broader than that in humans but the specificity of MBr1 reactivity was confirmed by competition assay with a synthetic tetrasaccharide that mimics the CaMBr1 antigen. On FACS analysis, only one of two clonal derivatives of the rat breast carcinoma line RAMA 25 expressed CaMBr1, and a negative cell subset was evident in repeated experiments. By contrast, both colon carcinoma lines, DHD/K12 and CC531, showed staining with MBr1, albeit at different levels of intensity, and no evidence of a negative subset. The cell line CC531 maintained or even increased CaMBr1 expression levels following transplantation in syngeneic immunocompetent animals. Our data suggest the usefulness of the rat as a test model for vaccines against human cancers overexpressing the CaMBr1 antigen.
Adobati
E
E
Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy.
Zacchetti
A
A
Perico
M E
ME
Cremonesi
F
F
Rasi
G
G
Vallebona
P S
PS
Hagenaars
M
M
Kuppen
P J
PJ
Pastan
I
I
Panza
L
L
Russo
G
G
Colnaghi
M I
MI
Canevari
S
S
D000818:Animals; D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D001940:Breast / Q000166:cytology / Q000378:metabolism; D019496:Cancer Vaccines; D002371:Cat Diseases / Q000378:metabolism* / Q000473:pathology; D002415:Cats; D004064:Digestive System / Q000166:cytology / Q000378:metabolism; D004283:Dog Diseases / Q000378:metabolism* / Q000473:pathology; D004285:Dogs; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D015674:Mammary Neoplasms, Animal / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*
D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines