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, 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

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.

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