A next-generation engineered T cell therapy for cancer
Triumvira Immunologics is a biotechnology company developing a novel platform for engineering T cells to attack cancers. In order to do this, we, like others, remove white blood cells from patients, use genetic engineering to direct T cells, which are an important component of the immune system, to recognize a protein found on the surface of certain cancer cells. We then expand these reprogrammed T cells so they can be administered back to the patient, where they will find the cancer cells and kill them. We believe our innovative and proprietary technology, called the T cell-Antigen Coupler (or TAC), possesses advantages over other approaches because of the nature of the TAC construct.
Triumvira has licensed the TAC technology from the laboratory of Jonathan Bramson, PhD, of McMaster University in Hamilton, Ontario and we are currently supporting a broad research effort in Dr. Bramson’s lab. Our team is continuing to explore the biology and potential of TAC-T cells, developing TACs against a variety of cancer targets, and scaling up the manufacturing process. Our goal is to begin human testing of TAC T cells by early 2019. Our team and our network of academic and industry consultants brings broad industry experience and deep scientific understanding to the TAC program.
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.