Immutep Announces That ImmuFact(R) IMP321 Induces
Activation of a Wide Range of Human Effector Cytotoxic Cells
Research paper describes IMP321's potency as a new
immunopotentiator in cancer patients
Orsay, September 17, 2007 - Immutep S.A., a biopharmaceutical company
specialised in immunostimulatory and immunomodulatory treatments of cancer and
infectious or autoimmune disease, announced today the publication of a
research paper showing that its lead product, IMP321, induces activation of a
wide range of human effector cytotoxic cells.
ImmuFact(R) IMP321 is a potent natural human immunostimulatory factor designed
to amplify the T cell immune response. It can be used either as an
immunopotentiator in therapeutic vaccines or alone at higher doses as a
monotherapy or in combination with chemotherapy. Six clinical trials have been
initiated with ImmuFact IMP321 in the last 30 months.
Immutep's ImmuFact research team carried out the study described in the
research paper at its laboratories near Paris.
The principal anti-tumour immune response is mediated through the activation
of type 1 cytotoxic (Tc1) CD8+ T cells, NK cells and monocytes/macrophages.
The research team investigated the potency of IMP321 at inducing such a
cytotoxic-type response in short term ex vivo assays on human blood cells.
The research team found that IMP321, a soluble recombinant form of the human
LAG-3 protein, binds to all circulating dendritic cells and a fraction of MHC
class II+ monocytes. Four hours after addition of IMP321 to blood cells these
antigen-presenting cells (APC) produce cytokines important for initiating the
immune response. At 18 hours, following this activation of the APC, a
significant number of CD8+ T cells and NK cells are fully activated in their
turn and produce Tc1 cytokines such as IFN-y or TNF-a. Similar induction was
observed in metastatic cancer patients.
In contrast to IMP321, TLR agonists, another class of immunostimulatory
factors, all induce the immunosuppressive IL-10 cytokine, and are therefore
unable to achieve the Tc1 IFN-y+ response that is crucial to an effective
anti-tumoral effect.
Thus, IMP321 has properties that confirm its uniqueness and potency as a new
immunopotentiator in cancer patients.
"It is remarkable that 92 per cent of blood donors or patients respond at
clinically-significant levels to a first short exposure of IMP321." said
Chrystelle Brignone, ImmuFact Project Manager and first author of the paper.
"This timely and orderly activation of both innate and adaptive immunity by
this potent endogenous APC activating agent shows great promise for a new era
of more effective immunotherapies in cancer patients," said Frédéric Triebel,
Immutep's Scientific and Medical Director. "Similar strong induction of both
innate and adaptive immunity effector arms has been already observed with
IMP321 administered for six months in metastatic cancer patients, without side
effects. This shows that immune activation could be safely induced over a long
period of time to high levels using this unique and natural signalling pathway
into APC."
For further information please visit the web-site
www.immutep.com
or e-mail John Hawken, CEO, at
JBHawken@immutep.com .
Notes to Editors:
The Published Paper
"A Soluble Form of Lymphocyte Activation Gene-3 (IMP321) Induces
Activation of a Large Range of Human Effector Cytotoxic Cells", Chrystelle
Brignone, Caroline Grygar, Manon Marcu, Knut Schäkel, and Frédéric Triebel,
Journal of Immunology 2007 179: 4202-4211
The LAG-3 Immune Control Mechanism
The Lymphocyte Activation Gene-3 (LAG-3) immune control mechanism plays a
role in both the upregulation of the immune system through antigen presenting
cells like dendritic cells and in the downregulation of the immune system
through different types of lymphocytes. The lymphocyte activation gene-3
(LAG-3 or CD223) binds to the MHC class II molecule which is at the centre of
immune response induction. LAG-3 is evolutionarily related to CD4 and has
retained an affinity 2 log higher than CD4 for their common ligand, MHC class
II molecules on antigen presenting cells such as dendritic cells. LAG-3 was
discovered by Frédéric Triebel. Immutep has an exclusive licence to the
molecule and related applications.
MHC class II
MHC Class II molecules are found only on a few specialised cell types,
including monocytes and dendritic cells, all of which are professional
antigen-presenting cells (APCs). Initially it was thought that their only role
was to present antigens to CD4+ T cells but it later became clear that they
also play a major role in mediating the competence of the immune response and
cooperation among different immune cells. They are extremely polymorphic
families of glycoproteines including the -DR, -DQ and -DP designations, of
which HLA-DR is most studied. Some of these glycoproteins are associated with
certain diseases of immune aetiology (e.g. auto-immune diseases like
diabetes).
Immutep S.A.
Immutep S.A. is a biopharmaceutical company developing immunostimulatory
factors for the treatment of cancer and chronic infectious diseases and
immunomodulatory therapeutic antibodies for the treatment of cancer or
autoimmune disease. The Company's technologies are based on a key immune
control mechanism that mediates T cell immune responses. Immutep is developing
its products both in-house and in partnership with pharmaceutical and biotech
companies. The Company was formed in 2001 by Frédéric Triebel, the scientific
founder, and John B. Hawken, a specialist in the management of biotech
companies, and has its headquarters and research facilities near Paris,
France. Immutep is backed by the Paris-based venture capital firm Innoven
Partenaires and the venture capital fund H2I, a specialist biotech fund
managed by Unicorn Biotutors/Equitis (Paris).
The Technologies
The Company's range of products is derived from LAG-3 (CD223), an
immunomodulatory protein expressed on the surface of activated T cells. The
unique proprietary product platforms make use of the key roles played by this
natural human protein in the regulation of the immune system.
ImmuFact(R)- T cell Immunostimulatory Factors for amplifying the T cell
response
The lead product, ImmuFact(R) 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 (DC). This
binding leads to DC 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 when IMP321
is coinjected with antigens or alone.
IMP321 is currently being tested by a wide range of therapeutic vaccine
companies as an adjuvant to their proprietary technologies.
Clinical Development
Immutep has completed two randomised single-blind escalating-dose Phase I
studies in 108 healthy individuals with IMP321 alone and combined with two
well-defined standard types of antigens to show safety of the product alone
and as an adjuvant in therapeutic vaccines. Four new clinical trials are in
progress: a Phase I/II clinical trial in metastatic renal cell carcinoma with
IMP321 injected alone, a Phase I/II study in metastatic breast cancer
combining IMP321 with paclitaxel in a chemoimmunotherapy protocol, a
disease-free melanoma study with IMP321 as an adjuvant to peptide antigens and
a lympho-depletive/adoptive transfer metastatic melanoma study.
For further information, please contact:
Andrew Lloyd & Associates
Andrew Lloyd / Neil Hunter
Tel: +44 1273 675100
allo@ala.com
/ neil@ala.com
