Definition

An off-the-shelf (OTS) preparation of induced pluripotent stem cell (iPSC)-derived, multiplexed-engineered alpha-beta T lymphocytes expressing a chimeric antigen receptor (CAR), using a specific H2CasMab-2 binder and Trac-mediated 1XX CAR, with a specific binding domain targeting the tumor-associated antigen (TAA) human epidermal growth factor receptor type 2 (HER2; EGFR2; ErbB2), with potential antineoplastic activity. FT825 contains seven synthetic controls in order to manipulate cellular function, including a CXC chemokine receptor 2 (CXCR2) to promote cell trafficking, a chimeric tumor growth factor-beta (TGFb) signal redirection receptor (TGFb-SRR) to redirect immunosuppressive signals, such as the immunosuppressive TGFb, in the tumor microenvironment (TME), a CD38 knock-out (CD38 null) to improve persistence, a synthetic interleukin (IL) 7/IL-7 receptor fusion protein (IL-7RF) to promote T-cell stemness, a T-cell receptor (TCR) removal to reduce the risk of graft-versus-host disease (GvHD), and a high-affinity non-cleavable CD16a receptor (hnCD16) to enable CD16-mediated antibody-dependent cellular cytotoxicity (ADCC) upon administration of a specific therapeutic antibody. Upon administration, allogeneic anti-HER2 CAR T cells FT825 target, bind to and induce selective toxicity in HER2-expressing tumors cells. This may result in the inhibition of tumor cell proliferation. HER-2 is overexpressed in various tumor cell types.