TLR Technology / Scientific Background

Agonists

Agonists of TLRs are compounds that stimulate, or "turn on", the innate immune system. This is the first line of defense and is later fortified by the specific adaptive immune system. Natural agonists for TLR are typical components of bacterial or viral origin such as flagella, lipopolysaccharides, bacterial lipoproteins and peptides, or certain nucleotide sequences of RNA or DNA.

MBiotec TLR 2/6 Agonist Program

MBiotec is currently developing the TLR agonist MALP-2S. MALP-2S is a patent-protected novel TLR 2/6 agonist. TLR agonists represent a new promising therapeutic approach not based on inhibiting the cell cycle, with the well-known side effects on fast growing cells of e.g. the bone marrow or intestine. TLR agonists are thought to interfere in at least two ways with the growth of cancer cells, by activating the innate immune system, and by warning the adaptive immune system so as to break immunological tolerance to the cancer cells, thus recruiting cytolytic T-lymphocytes to act against the cancer.

MALP-2S induces the release of various chemokines and cytokines from macrophages, dendritic and other cells. This leads to an influx and activation of dendritic cells, macrophages, natural killer cells and T-cells around the area of application. It is hypothesized that MALP-2S, in addition to initially killing tumor cells by means of natural killer cells and macrophages, lastingly leads to activation of anergic dendritic cells and thus abolishes tumor tolerance.

MALP-2S was shown to be effective in animal models for pancreatic cancer. An open-label study in terminally ill pancreatic carcinoma patients has indicated prolongation of survival as compared to patients treated with standard chemotherapy.

MALP-2 is applied locally (by ultrasonic-guided injection) which is a standard technique familiar to physicians with experience in oncology.

Figure: Simplified diagram of the toll-like receptor triggering. It focuses on one pathway i.e. the activation of the transcription factor NF kappa B which is downstream of all TL- receptors but represents only one of many transcription factors activated by TLR agonists. Triggering of different TL- receptors may involve separate pathways and does not lead to an identical response. For details of the MALP-2S pathway see also
www.malp-research.de/malp_signal_pathway.html