Induction of humoral and cellular responses in cynomolgus monkeys immunised with mannan-human MUC1 conjugates.
Mice immunised with oxidised mannan conjugated to the human mucin 1 (MUC1), produce MHC Class 1 restricted CD8+ cytotoxic T-cells which eradicate MUC1 + tumours, indicating potential for the immunotherapy of MUC1 + cancers in humans. We now describe preclinical studies performed in cynomolgus monkeys immunised with human or murine MUC1 conjugated to oxidised mannan, where immune responses and toxicity were examined. High titred antibodies specific for MUC1 were produced, MUC1 specific CD4+ and CD8+ T-cell proliferative responses and specific cytotoxic precursor cells (CTLp) were found, but not MUC1 specific cytotoxic T-cells (CTL). There was no toxicity and monkeys can be immunised against human MUC1 with mannan-MUC1 conjugates, but a humoral response (Th2 type) predominates. The results contrast with those obtained in mice when a CTL response (Th1 type) predominates.
Vaughan
H A
HA
Austin Research Institute, Austin and Repatriation Medical Centre, Heidelberg, Vic., Australia.
Ho
D W
DW
Karanikas
V A
VA
Ong
C S
CS
Hwang
L A
LA
Pearson
J M
JM
McKenzie
I F
IF
Pietersz
G A
GA
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D003520:Cyclophosphamide / Q000494:pharmacology; D004187:Disaccharides / Q000276:immunology; D018604:Epitope Mapping; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation; D008252:Macaca fascicularis; D008351:Mannans / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D018074:Vaccines, Conjugate / Q000276:immunology
D004187:Disaccharides; D008351:Mannans; D018396:Mucin-1; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; C055075:galactosyl-(1-3)galactose; D003520:Cyclophosphamide