In adoptive cell therapy, the infusion of donor-derived T cells to cancer patients with a different background then that of the donor leads to multiple reactions, including the donor cells attacking the patient’s healthy tissue, known as Graft-versus-Host disease (GvHD) as well as the rejection of the therapy by the patient’s immune system known as Host-versus-Graft (HvG) reaction.

The key molecule principally responsible for GvHD is the T cell receptor (TCR), a molecule present at the surface of T cells. At the center of allogeneic CAR T therapy, the goal is to eliminate or blunt the signaling of the TCR through engineering with a specific technology. By reducing the signaling of the TCR, the engineered allogeneic CAR T cells fail to recognize the patient’s healthy tissue as foreign leading to an absence of GvHD.

Celyad Oncology’s non-gene edited technologies TIM and shRNA offer this potential. Through the co-expression of either technology with specific CAR of interest, we can design cell therapy candidates intended to inhibit the function of the TCR while allowing the T cells to target the cancer. In addition, shRNA technology may also offer the potential to avoid HvG, allowing the CAR T cells to persist longer in the patient offering the opportunity for improved outcomes.