Unique strategy to develop allogeneic CAR T
Celyad Oncology is pioneering a differentiated approach to the discovery and development of allogeneic, or off-the-shelf, CAR T cell therapy candidates for the treatment of cancer led by a pair of non-gene edited approaches including our T cell receptor Inhibitory Molecule (TIM) and short hairpin RNA (shRNA) technologies.
Our shRNA-based CYAD-200 series of CAR T candidates are currently in preclinical & early clinical development. The first candidate of the CYAD-200 series, CYAD-211, is currently in the Phase 1 IMMUNICY-1 trial for the treatment of relapsed/refractory multiple myeloma.
Celyad Oncology is advancing the field of allogeneic CAR T therapy by exploring two proprietary, non-gene edited technology platforms to target the TCR complex
Novel technology targeting the TCR underpins allogeneic CAR T cells
In adoptive cell therapy, the infusion of donor-derived T cells to cancer patients with a different background than 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 TCR (T cell receptor), 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.