Technology Platforms
- new classes of human protein immunostimulatory factors for the treatment of cancer and chronic infections (ImmuFact® and ImmuCcine®).
- therapeutic antibodies for the modulation of the immune system in cancer, autoimmune diseases and transplantation (ImmuTune®).
The Company is developing two complementary types of therapeutic proteins:
Each type of therapeutic is based on newly-discovered pathways involved in the Lymphocyte Activation Gene-3 (LAG-3) immune control mechanism, which plays a vital role in the regulation of the immune system. These pathways were discovered by the Company's scientific founder, Pr. Frédéric Triebel, initially developed in collaboration between the Institut Gustave Roussy and Merck-Serono, and then confirmed by several independent teams.
This has enabled Immutep to build a distinctive platform providing diversified risks and opportunities while maintaining scientific focus.
Immunostimulatory Factors:
A soluble LAG-3 protein is a high affinity MHC class II ligand that strongly stimulates the immune response. IMP321 is a recombinant soluble human LAG-3Ig fusion protein. MHC class II proteins play a fundamental role in life-essential processes and are associated with many areas of biology and medicine. One important feature of MHC class II proteins is their recognition by the immune system. Research has demonstrated that the MHC class II proteins expressed at the surface of antigen presenting cells, such as dendritic cells, monocytes, macrophages or B lymphocytes are key elements for antigen recognition (self/non-self discrimination) as well as the development of appropriate T cell responses. Many aspects of the immune system can be activated by soluble LAG-3 proteins, giving rise to greatly enhanced cellular (e.g. T cell) responses. In particular, one type of immune response, mediated by cytotoxic T lymphocytes (CTL), or "killer cells," can be effectively triggered by MHC class II+ dendritic cells activated by LAG-3 proteins. These CTL are thought to be one of the body's most potent defenses against diseased cells, such as those infected by viruses or altered by cancer.
ImmuFact®: Natural T-Cell Immunostimulants
The induction of the T cell response depends on the ability of specialised "antigen presenting cells" to present the antigen to the receptors on T-cells ("antigen presentation"). This both stimulates the T-cells ("T cell priming") and enables them to recognise the pathogen. LAG-3 plays a central role in this process.
The lead product, ImmuFact® IMP321, is a highly potent T cell immunostimulatory factor. It is a soluble form of LAG-3 that binds, with high affinity, to MHC class II molecules expressed by dendritic cells and monocytes. This binding leads to dendritic cells maturation, migration to the lymph nodes and enhanced cross-presentation of antigens to T cells. As a result, strong and sustained anti-tumour or anti-viral cytotoxic T cell responses are obtained.
IMP321 has two intended clinical settings:
– low dose (e.g. 250 µg) as adjuvant to cancer vaccines
– high dose (e.g. 12 injections 6 mg s.c.) combined with standard chemotherapy (first-line chemo-immunotherapy).
ImmuCcine®: Vectorisation of T-Cell Antigens: "one molecule, two functions"
Covalently linking an antigen to IMP321 in a fusion protein results in both vectorisation of the antigen to dendritic cells as well as the immunostimulatory effect described above. Vectorised therapeutic vaccines have been obtained by Immutep’s researchers by genetically coupling antigens to IMP321 leading to rapid capture and internalisation of the antigen into dendritic cells with increased efficacy and lower dose of vaccine to be used per injection. This second technology thereby combines the T-cell immunostimulatory effect with a powerful vectorisation effect (i.e. one molecule, two functions).
Therapeutic Antibodies:
ImmuTune®: Fine Tuning of the Immune Response
This technology comprises antibodies against LAG-3 in its natural membrane-bound form on the surface of T cells:
- ImmuTune antagonist antibodies which inhibit the role of LAG-3 as a down-regulator of the T cell response. LAG-3 down-regulates the T cell response either directly by inhibiting effector T cells or indirectly through the suppressive activity of the LAG-3+ Tregs. Thus antagonist antibodies lead to enhanced T cell proliferation. Such antibodies can be used alone or in combination with therapeutic vaccines.
- ImmuTune depleting antibodies. This application is based on the fact that LAG-3 is, by definition, a marker of activated T cells enabling depleting antibodies to suppress unwanted T cell activity in autoimmune diseases or transplantation. The lead product, IMP731, will enter the clinic in 2012.
