TRAMMICS: Target Receptor Activating Membrane Moiety
with Inert Cytoplasmic Stub
Chimeric antigen receptors (CARs), are engineered receptors that combine new specificity for cells. Typically, these receptors graft the specificity of a monoclonal antibody onto T-cells (named CAR-T) and are used to improve their targeting properties. While the primary use of cell therapy based CAR-T is in cancer, the potential of this technology may be expanded to many other markets with huge unmet medical need like that of autoimmunity and the Central Nervous System (CNS). Throughout the last decade, Prof. Monsonego’s lab has been focusing in studies characterizing the therapeutic potential of CD4 T-cells in neurodegenerative and autoimmune diseases. This is due to the unique capability of T-cells to migrate into and within the brain and other tissues in search for antigens as part of immune surveillance as well as the T-cells remarkable immune-modulating effects of the cells. His studies revealed the molecular mechanism by which the T-cells cross the brain ventricles and migrate within the brain targeting amyloid plaques in animal models of Alzheimer’s disease (AD), modulating inflammation and promoting neural repair. Based on these initial findings, a novel idea has been brought forth to specifically direct T-cells to activate rather than kill target cells in a trophic manner.
Target Receptor Activating Membrane Moiety with Inert Cytoplasmic Stub (TRAMMICS), encompasses expressing a CAR by mean of a single chain agonist antibody fragment or a ligand on the T-cell membrane. The T-cell can then target in an agonistic manner a receptor on various cells such as neurons, pancreatic cells and potentially others. Our goal is to use T-cells with the antibody/ligand membrane moiety to specifically activate or inactivate a receptor on tissue-specific target cells and thereby initiate a repair program.
- An ultimate platform approach for promoting repair in cell/tissue of choice.
- Overcome the limited capacity of big molecules to cross the blood-brain-barrier or diffuse properly within parenchymal tissues.
- Long-term site-specific and multi-factorial effects as opposed to short half-life and limited efficacy of soluble molecules
- A personalized approach which avoids an immune response that often neutralize modified drugs
PCT patent No. PCT/IL2017/051133 filed October 2, 2019
National phase entry in: Australia, China, Israel, Europe, Hong Kong and USA