IMP321's potency as a new immunopotentiator in cancer patients

Biopharmaceutical company Immutep has published a research paper showing that its lead product IMP32 induces activation of a wide range of human effector cytotoxic cells.

The paper - A Soluble Form of Lymphocyte Activation Gene-3 (IMP321) Induces Activation of a Large Range of Human Effector Cytotoxic Cells - highlights 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.

Researchers found that 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.

ImmuFact IMP321 is a 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.

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.

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.

"It is remarkable that 92% 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 - A Soluble Form of Lymphocyte Activation Gene-3 (IMP321) Induces Activation of a Large Range of Human Effector Cytotoxic Cells.

"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 Frederic 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."