In head-to-head comparisons of HER2-directed TAC-T cells to CAR-T cells, TAC-T cells outperformed CAR-T cells on multiple parameters. In cell-killing assays, TAC-T cells demonstrated superior killing of cancer cells compared to CAR-T cells. When administered to immunodeficient (NRG) mice bearing human tumor xenografts, TAC-T cells were able to reduce or eliminate tumors that had been established for 30 days with no signs of toxicity. In contrast, the HER2-directed CAR-T cells were highly toxic in the mice, usually resulting in lethality within days of administration and accompanied by an over-exuberant and dysregulated cytokine profile (including secretion of high levels of interleukin-4 and interleukin-10) compared to the cytokine profile exhibited by the TAC-T cells. In those cases in which mice survived the CAR-T cell toxicity, the anti-tumor effect of the CAR-T cells was delayed and inferior to that of TAC-T cells.
Thus, we have established that TAC-T cells possess a distinct biology from CAR-T cells that results in a more robust and less toxic anti-tumor response, in this solid tumor model. We believe this offers great promise for the clinical development of TAC-T cells and for the cancer patients who may eventually benefit from this therapy.
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.