Antibody and T cell responses of patients with adenocarcinoma immunized with mannan-MUC1 fusion protein

V Karanikas; L A Hwang; J Pearson; C S Ong; V Apostolopoulos; H Vaughan; P X Xing; G Jamieson; G Pietersz; B Tait; R Broadbent; G Thynne; I F McKenzie

doi:10.1172/JCI119825

Antibody and T cell responses of patients with adenocarcinoma immunized with mannan-MUC1 fusion protein

J Clin Invest. 1997 Dec 1;100(11):2783-92. doi: 10.1172/JCI119825.

Authors

V Karanikas¹, L A Hwang, J Pearson, C S Ong, V Apostolopoulos, H Vaughan, P X Xing, G Jamieson, G Pietersz, B Tait, R Broadbent, G Thynne, I F McKenzie

Affiliation

¹ Immunology and Vaccine Laboratory, The Austin Research Institute, Heidelberg 3084, Victoria, Australia.

PMID: 9389743
PMCID: PMC508483
DOI: 10.1172/JCI119825

Abstract

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.

Publication types

Clinical Trial
Clinical Trial, Phase I
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / immunology*
Adenocarcinoma / physiopathology
Aged
Amino Acid Sequence
Antibodies / immunology*
Breast Neoplasms / immunology*
Breast Neoplasms / physiopathology
Cancer Vaccines / immunology*
Cell Division
Colonic Neoplasms / immunology*
Colonic Neoplasms / physiopathology
Cytotoxicity Tests, Immunologic
Epitopes, B-Lymphocyte / immunology
Female
Humans
Immunoglobulin Isotypes
Male
Mannans / administration & dosage
Mannans / immunology*
Molecular Sequence Data
Mucin-1 / administration & dosage
Mucin-1 / immunology*
Recombinant Fusion Proteins / administration & dosage
Recombinant Fusion Proteins / immunology
Rectal Neoplasms / immunology*
Rectal Neoplasms / physiopathology
Stomach Neoplasms / immunology*
Stomach Neoplasms / physiopathology
T-Lymphocytes / cytology
T-Lymphocytes / immunology*

Substances

Antibodies
Cancer Vaccines
Epitopes, B-Lymphocyte
Immunoglobulin Isotypes
Mannans
Mucin-1
Recombinant Fusion Proteins