Publications & Reports

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

Karanikas V, Hwang LA, Pearson J, Ong CS, Apostolopoulos V, Vaughan H, Xing PX, Jamieson G, Pietersz G, Tait B, Broadbent R, Thynne G, McKenzie IF
Immunology and Vaccine Laboratory, The Austin Research Institute, Heidelberg 3084, Victoria, Australia.

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

  • Journal: The Journal of Clinical Investigation
  • Published: 01/12/1997
  • Volume: 100
  • Issue: 11
  • Pagination: 2783-2792

Authors