Antibody and T cell responses of patients with adenocarcinoma immunized with mannan-MUC1 fusion protein.
Mucin 1 (MUC1) is a large complex glycoprotein that is highly expressed in breast cancer, and as such could be a target for immunotherapy. In mice, human MUC1 is highly immunogenic, particularly when conjugated to mannan, where a high frequency of CD8(+) MHC-restricted cytotoxic T lymphocytes is induced, accompanied by tumor protection. On this basis, a clinical trial was performed in which 25 patients with advanced metastatic carcinoma of breast, colon, stomach, or rectum received mannan-MUC1 in increasing doses. After 4 to 8 injections, large amounts of IgG1 anti-MUC1 antibodies were produced in 13 out of 25 patients (with antibody titers by ELISA of 1/320-1/20,480). Most of the antibodies reacted to the epitopes STAPPAHG and PAPGSTAP. In addition, T cell proliferation was found in 4 out of 15 patients, and CTL responses were seen in 2 out of 10 patients. Mannan-MUC1 can immunize patients, particularly for antibody formation, and to a lesser extent, cellular responses. It remains to be seen whether such responses have antitumor activity.
Karanikas
V
V
Immunology and Vaccine Laboratory, The Austin Research Institute, Heidelberg 3084, Victoria, Australia.
Hwang
L A
LA
Pearson
J
J
Ong
C S
CS
Apostolopoulos
V
V
Vaughan
H
H
Xing
P X
PX
Jamieson
G
G
Pietersz
G
G
Tait
B
B
Broadbent
R
R
Thynne
G
G
McKenzie
I F
IF
D000230:Adenocarcinoma / Q000276:immunology* / Q000503:physiopathology; D000368:Aged; D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology* / Q000503:physiopathology; D019496:Cancer Vaccines / Q000276:immunology*; D002455:Cell Division; D003110:Colonic Neoplasms / Q000276:immunology* / Q000503:physiopathology; D003601:Cytotoxicity Tests, Immunologic; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D007132:Immunoglobulin Isotypes; D008297:Male; D008351:Mannans / Q000008:administration & dosage / Q000276:immunology*; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000008:administration & dosage / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D012004:Rectal Neoplasms / Q000276:immunology* / Q000503:physiopathology; D013274:Stomach Neoplasms / Q000276:immunology* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000906:Antibodies; D019496:Cancer Vaccines; D018985:Epitopes, B-Lymphocyte; D007132:Immunoglobulin Isotypes; D008351:Mannans; D018396:Mucin-1; D011993:Recombinant Fusion Proteins