Paris, March, 2nd, 2001
Collaboration between immunologists and chemists at the Institut Pasteur led to the development of a synthetic immunogen that allows rejection of implanted tumor cells. This work, published in " The Journal of Immunology ", is a crucial step in immunotherapy against cancers.
Identification of tumor-associated antigenes has opened up a basis for cancer therapeutic vaccines. Among them, the highly expressed Tn antigene is present in numerous cancers such as prostate, colorectal, breast and lung cancers.
At the Institut Pasteur, Claude Leclerc, head of the Biology of Immune Regulations Unit, and Sylvie Bay's group, in the Organic Chemistry Unit, have developed a fully synthetic immunogen, MAG (Multiple Antigenic Glycopeptide). It carries the Tn tumoral antigen associated to a peptide promoting cellular immune responses, and is linked to a peptide backbone.
This synthetic immunogen appears to be very efficient to induce anti-tumoral antibody responses when injected in mice. MAG induced antibodies recognize murine as well as human tumor cell lines expressing the Tn antigen.
Prophylactic vaccination using MAG provided protection of mice against tumor challenge, ranged from 70-90% depending on the dose of MAG used for vaccination. Moreover, treatment with this synthetic immunogen promoted up to 80% survival rate of tumor-bearing mice.
Based on these promising results, development of synthetic vaccines for human therapeutic treatment and tests on humanised mice are in progress.
The strategy used for immunogen synthesis offers many advantages, when compared to traditional conjugates, ie :
- the core matrix is non-immunogenic therefore immune responses are exclusively directed against the tumoral antigen
- the structure of the Tn antigen is designed to be closely related to the native state in tumor cells
- the construction has a well-defined chemical structure securing potential downstream use in human therapy.
Altogether, these results provide new insight into therapeutic vaccines against cancers and infectious diseases as well. In addition, therapeutic vaccination offers a new dimension to traditionnal vaccination.
- Claude LECLERC, tel : 33 1 45 68 86 18 - Biology of Immune Regulations Unit
E-mail : firstname.lastname@example.org
- Richard LO-MAN, tel : 33 1 45 83 52 - Biology of Immune Regulations Unit
E-mail : email@example.com
- Sylvie BAY , tel : 33 1 45 68 83 97 - Organic
E-mail : firstname.lastname@example.org
- Press Office
Tel : 33 1 45 68 81 47 E-mail : email@example.com
"Anti-Tumor Immunity Provided by a Synthetic Multiple Antigenic Glycopeptide Displaying a tri-Tn Glycotope", The Journal of Immunology, 2001, 166
Richard Lo-Man1, Sophie Vichier-Guerre 2, Sylvie Bay 2, Edith Dériaud 1, Danièle
Cantacuzène 2 & Claude Leclerc 1
1 Unité de Biologie des Régulations Immunitaires, Institut Pasteur, Paris
2 Unité de Chimie Organique, Institut Pasteur, Paris