Immutep Announces That ImmuFact(R) IMP321 Has Entered A Phase I Lymphodepletion Therapeutic Vaccine Trial In Metastatic Melanoma

Main Category: Melanoma / Skin Cancer
Also Included In: Clinical Trials / Drug Trials;  Immune System / Vaccines
Article Date: 30 Aug 2007 - 1:00 PST

email to a friend   printer friendly   view / write opinions   rate article

Immutep S.A., a biopharmaceutical company specialised in immunostimulatory and immunomodulatory treatments of cancer and infectious or autoimmune disease, announced that its lead product, ImmuFact(R) IMP321, has entered a Phase I clinical trial in metastatic melanoma in a novel protocol combining adoptive T cell transfer after transient lymphodepletion associated with peptide vaccination.

ImmuFact(R) IMP321 is a potent natural human T cell 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. This new study is the sixth clinical trial with ImmuFact IMP321 in 30 months.

The Fondation du Centre Pluridisciplinaire d'Oncologie, in cooperation with the Ludwig Institute for Cancer Research, both in Lausanne, is conducting the clinical study. The design is an open-label single-arm trial assessing the use of IMP321 as an adjuvant to amplify the expansion of antigen-specific CD8 T cells following transient immunosuppression and adoptive T cell transfer in patients with advanced melanoma.

The protocol involves depleting the patient's lymphocytes using chemotherapy and then reinjecting autologous peripheral mononuclear cells including tumour-specific CD8 T cells. In order to further amplify the anti-tumour immune response during homeostatic proliferation in the immune reconstitution period, the patient also follows a course of treatment with a therapeutic cancer vaccine containing a peptide melanoma antigen (Melan-A/MART1) and IMP321 as well as incomplete Freud's adjuvant. The primary objectives will be to evaluate safety and immunological efficacy.

The study is being carried out by Professor Serge Leyvraz, MD and Dr. Verena Voelter, MD as Principal Investigators with Professor Daniel Speiser, MD, Professor Pedro Romero, MD and Dr Julien Laurent, PhD as co-investigators. These teams in Lausanne are pioneering the use of lymphodepletion and adoptive T cell transfer associated with cancer vaccines in Europe.

"We are very pleased to start this trial in metastatic melanoma patients which should provide information about the potency of IMP321 as an adjuvant for the induction of specific antitumour CD8 T cell (CTL) responses after lymphodepletion and adoptive T cell transfer," said Dr Verena Voelter, one of the PIs of this study. "The concept of transient immunosuppression combined with the stimulation of an antigen-specific antitumour response during the immune reconstitution period has been shown to be very promising in preclinical animal models as well as in first clinical trials run in melanoma patients in the US."

"We are delighted to announce another cancer vaccine trial using our immunopotentiator agent, IMP321," said Frédéric Triebel, Scientific & Medical Director of Immutep. "This new class of non-TLR agonist may represent the extra boost that peptide antigens need for a strong and prolonged CTL activity".

Lymphodepletion and adoptive transfer of T cells in the treatment of cancer

This protocol investigates the association of transient immunosuppression using a single cycle of a conditioning regimen with cyclophosphamide and fludarabine, followed by the adoptive transfer of antigen- (tumour-, Melan-A) specific CD8 T cells and peptide vaccination with Melan-A for patients with advanced melanoma. The rationale of this study is to induce homeostatic proliferation of the tumour specific T cells during the immune reconstitution period after immunosuppression. The protocol is designed for patients who either have a spontaneous specific immune response against the antigen Melan-A/MART1 or have undergone prior specific immuno-monotherapy with the same epitope. Encouraging results have been achieved by the team in Lausanne and by other teams in the USA.

Fondation du Centre Pluridisciplinaire d'Oncologie, Lausanne

The Fondation du Centre Pluridisciplinaire d'Oncologie, Lausanne, is one of the major comprehensive cancer centres in Europe. The Centre in co-operation with the Ludwig Institute of Cancer Research is running several immunotherapy trials in melanoma and has a long experience in therapeutic approaches in cancer and in translational research.

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 start-ups, 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 clinical trials are in progress: a Phase I clinical trial in metastatic renal cell carcinoma with IMP321 injected alone, a Phase I 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 the current metastatic melanoma study.

http://www.immutep.com