Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Prophylactic and therapeutic vaccination using a fully synthetic immunogen displaying the saccharidic Tn antigen

R Lo-Man PhD, S Vichier-Guerre PhD 2, S Bay PhD 2, E Deriaud, C Leclerc PhD 1

1 Dept Immunology,, 2 Unit of Organic Chemistry, Institut Pasteur, Paris, France,

AIMS: Aberrant glycosylation of mucins leads to the exposure of cryptic carbohydrate antigens at the surface of carcinoma cells which make them good targets for immune intervention. Identification of cancer associated glycotopes as well as progresses in chemical synthesis has opened up the way for the development of fully synthetic immunogens that can induce anti-saccharidic immune response. METHODS: We designed a multiple antigenic O-linked glycopeptide system (MAG) and chemically synthesized MAGs carrying a CD4+ T cell epitope associated with various glycotopes corresponding to the carcinoma-associated Tn antigen. These MAGs were tested for the induction of Tn-specific antibodies and in prophylactic vaccination and therapeutic protocols using the TA3/Ha carcinoma mouse model. RESULTS: The antibodies induced by our MAGs recognized murine and human tumor cell lines expressing the Tn antigen. Prophylactic vaccination using MAG provided protection of mice against tumor challenge. When used in active specific immunotherapy (ASI), MAG efficiently promoted the survival of tumor-bearing mice. However, the MAG carrying a tri-Tn glycotope was much more efficient than the mono-Tn analogue in promoting the survival of tumor-bearing mice. Furthermore, in ASI, a linear glycopeptide carrying two copies of the tri-Tn glycotope was shown to be poorly efficient as compared to the dendrimeric MAG. CONCLUSIONS: Our results show that both the clustering of carbohydrate antigens and the way they are displayed seem to be important parameters for the elaboration of fully synthetic immunogens aiming at the stimulation of protective anti-saccharidic immune responses against tumor antigens.

KEY WORDS: immunotherapy.

For more information, contact

Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on immunotherapy.