TruUCAR is our proprietary technology platform for generating high-quality allogeneic CAR-T therapies that can be administered “off-the-shelf” at lower cost. Unlike autologous CAR-T therapies, these products use T cells from non-HLA-matched healthy donors, making them readily available to treat cancer patients, including those who are less suitable for, or have relapsed after, autologous CAR-T cell therapy as well as those with rapidly progressing cancer.
To reduce host-versus-graft rejection (HvG), we engineer T cells to express a CAR that specifically targets a patient’s own T and natural killer (NK) cells (alloreactive killer cells) that would otherwise be directed against the foreign, or allogeneic, CAR-T cells, resulting in rejection by the patient without affecting the recovery of other immune cell compartments during treatment. This feature allows our allogeneic cell therapies to survive in a patient’s immune system without the need for combination treatment with anti-CD52 antibodies that may leave that patient at risk for infection.
To reduce the possibility of graft-versus-host disease GvHD from allogeneic T cells, we utilize CRISPR/Cas9 to disrupt the T cell receptor alpha constant (TRAC) locus to eliminate surface expression of the TCR complex of our TruUCAR product candidates. Furthermore, to eliminate potential fratricide (self-killing of CAR-T cells during the production process), we utilize CRISPR/Cas9 to disrupt CD7, a pan T and NK marker on the CAR-T cells.
Since TruUCAR is modular, alternative CAR constructs targeted against different antigens can be applied to TruUCAR to achieve similar therapeutic effects. For example, the anti-HvG and anti-GvHD functions can be carried out by a dual CAR design or a single CAR design for dual functions.
In the case of a dual CAR design, one CAR serves a “defensive” purpose, targeting the patient’s own alloreactive killer T cells and NK cells while the second CAR serves an “attack” purpose, targeting tumor antigen to eradicate tumor cells. In the case of a single CAR design, the CAR carries out dual functions, targeting both alloreactive killer T cells and NK cells, as well as T cancer cells.
Our donor-derived CAR produces allogeneic CAR-T cells based on HLA-matching, offering an alternative CAR-T cell therapy option for patients who are less suitable for autologous CAR-T cell therapies. Produced from T cells of the patients themselves, autologous CAR-T cells may be of lower quality with compromised tumor killing ability due to repeated radiotherapy and chemotherapy. Our donor-derived CAR technique is designed to derive higher quality T cells from healthy donors to manufacture CAR-T cells that demonstrate better tumor clearance ability as well as improved response rate and persistence of efficacy.