Immunization of colorectal cancer patients with modified ovine submaxillary gland mucin and adjuvants induces IgM and IgG antibodies to sialylated Tn.
Tn and sialylated Tn (sTn) are blood group-related epitopes expressed on mucins of colon carcinoma and other epithelial tumors and are, therefore, potential targets for immunological control. We have immunized 20 colorectal cancer patients at high risk for recurrence with a vaccine consisting of partially desialylated ovine submaxillary gland mucin (modified OSM) which contains both Tn and sTn determinants. Six patients were treated with modified OSM alone (group 1), eight patients were treated with modified OSM and the immunological adjuvant DETOX (group 2), and six patients were treated with modified OSM and Bacillus Calmette-Guérin (group 3). Pre- and postvaccination sera were tested by enzyme-linked immunosorbent assay and dot blot immune stains for antibodies reactive with modified OSM. Antibody titers increased in 4 of 8 patients immunized with modified OSM and DETOX, in 5 of 6 patients immunized with modified OSM and B. Calmette-Guérin, and in 0 of 6 patients receiving modified OSM without adjuvant. The specificity of induced IgM and IgG antibodies was confirmed by demonstrating reactivity with OSM, bovine submaxillary mucin, and synthetic glycoconjugates sTn-human serum albumin (HSA) and Tn-HSA in enzyme-linked immunosorbent assay and immune stains. Median IgM pre-postvaccination reciprocal titers were 20/80 for Tn-HSA and 10/320 for sTn-HSA. Low level IgG antibody titers against sTn-HSA were detected after vaccination in 7 patients. Toxicity was limited to inflammatory skin reactions at the site of vaccination resulting from the adjuvants. No inflammatory infiltrates were seen in the skin when the modified OSM vaccine was administered in the absence of an immunological adjuvant. These results demonstrate that sTn and Tn can be recognized by the human immune system and that vaccines containing these structures can be administered safely with immunological adjuvants. Attempts to augment the immunogenicity of these carbohydrate antigens by covalent attachment to immunogenic carrier proteins and the use of more potent immunological adjuvants are now being pursued.
O'Boyle
K P
KP
Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Zamore
R
R
Adluri
S
S
Cohen
A
A
Kemeny
N
N
Welt
S
S
Lloyd
K O
KO
Oettgen
H F
HF
Old
L J
LJ
Livingston
P O
PO
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000008:administration & dosage / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007106:Immune Sera / Q000032:analysis; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D009077:Mucins / Q000008:administration & dosage / Q000276:immunology*; D012756:Sheep; D013363:Submandibular Gland / Q000737:chemistry*; D014612:Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D007106:Immune Sera; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009077:Mucins; C040286:Tn antigen; D014612:Vaccines; C055491:sialosyl-Tn antigen