Three Functional Domains
The TAC construct was designed with the explicit intent of recapitulating a more “normal” activation of T cells than what is observed for CAR-T cells, by using the T cell receptor (TCR) instead of bypassing it.
In order to accomplish this, the TAC architecture features three functional domains. The first is a tumor targeting domain that might consist of a single chain antibody, a designed ankyrin repeat protein (DARPin), or some other targeting moiety. The second domain is also extracellular and is a single chain antibody that binds CD3, thus bringing the TAC receptor in close proximity to the rest of the TCR complex. The third domain consists of the transmembrane and cytoplasmic regions of the CD4 co-receptor that binds the protein kinase LCK , which phosphorylate immunoreceptors tyrosine-based activation motifs (ITAMs) on the TCR complex as one of the initial steps in T cell activation.
TAC-T Cell Manufacturing
The manufacture of TAC-T cells is similar to that of other engineered T cells. The process begins with a patient’s white blood cells, obtained through leukapheresis. The mononuclear cells, which include T cells, are separated from the other white blood cells. The T cells are activated and special virus called lentivirus is used to deliver DNA containing the TAC to the T cells. These cells are then expanded over the course of several days until there are hundreds of millions of cells or more, which are then frozen. When the patient returns for treatment, the TAC-T cells are thawed and administered intravenously.
Using TAC Technology to Attack Cancer Cells
At Triumvira Immunologics, we are reprogramming the immune system to attack cancer cells. In order to do this, we use genetic engineering to redirect T cells, an important component of the immune system, to recognize proteins found on the surface of cancer cells. We use T cells taken from a patient, engineer them to express our T cell-Antigen Coupler (TAC), then expand them and then administer the modified cells back to patients, where they will find the cancer cells and kill them. Triumvira’s TACs are a completely novel and innovative approach to reprogramming T cells, which we believe offer important advantages over the approach taken by other companies.