Engineering T Cells

The Engineered T cell Revolution

For more than two decades, scientists and clinicians have been trying to activate the immune system of cancer patients to attack and destroy tumors. The task has been challenging because the immune system has regulatory mechanisms that keep its destructive force directed towards foreign targets, like bacteria and viruses, and not the body’s own cells.  Also, cancer cells employ sophisticated tricks to avoid or quench immune system attacks.  But recent progress has been impressive, and one of the new strategies has been to engineer T cells to attack proteins found on the surface of cancer cells.  Impressive clinical results have been obtained with the Chimeric Antigen Receptor (CAR) technology, consisting of stimulatory domains that are capable of activating the T cell, which are fused to an antibody targeted against a cancer antigen of choice.

Clinical Successes Accompanied by Real and Important Toxicity

There have been a number of clinical trials showing that CAR-T cell therapies targeted towards CD19, a protein found on the surface of B cells and certain leukemias and lymphomas can generate responses and even long-term remissions in patients suffering from these malignancies.  Although the success of CD19 CAR-T cells in clinical trials has been striking, CAR-T cells directed against other kinds of tumors have not yet had the same level of success, although many programs are still early in development. There is an extensive effort underway to develop CAR-T cells targeting a variety of different sell surface antigens found on a wide variety of tumors.

Challenges for Engineered T Cells

Along with some impressive efficacy for CD19 targeted CAR-T cells, there have also been some significant toxicities for the CAR-T cells, falling into two categories:

  1. Activated T cells release cytokines that directly affect tumor cells and recruit additional immune system cells. CAR-T cells commonly release large amounts of cytokines, resulting in systemic toxicity called cytokine release syndrome (CRS). The use of anti-cytokine therapies can help manage but not eliminate the serious side effects of massive cytokine release.
  2. CAR-T cells are exquisitely sensitive to small amounts of the targeted cell surface antigen and so they can indiscriminately attack healthy and tumor cells alike, resulting in “on-target, off-tumor toxicity.” If the on-target, off-tumor reactivity destroys or damages essential tissues or results in overwhelming cytokine secretion, the side effects of that CAR-T cell therapy may be intolerable.

TACs are designed to provide a more regulated activation of T cells that offers the possibility of improved safety and potentially efficacy as well, by using the T cell’s natural activation pathways.

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.