drug_type
RELEVANT_DRUG
intervention_type
Cellular therapy (CAR T cells)
drug_description
Off-the-shelf, allogeneic iPSC-derived HER2-directed CAR T-cell therapy designed to kill HER2 (ERBB2)-expressing tumor cells.
nci_thesaurus_concept_id
C204108
nci_thesaurus_preferred_term
iPSC-derived Allogeneic Anti-HER2 CAR T-cells FT825
nci_thesaurus_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.
drug_category
CAR T
drug_class
Cellular Therapy
drug_delivery_route
Intravenous
drug_mechanism_of_action
Off-the-shelf, allogeneic iPSC-derived HER2-directed CAR T cells that recognize HER2 (ERBB2) via a 1XX CAR, triggering T-cell activation and cytotoxic killing of HER2+ tumor cells. Engineered features include CXCR2 to enhance trafficking, a TGFβ signal-redirection receptor to counter immunosuppression, CD38 knockout for persistence, an IL-7/IL-7R fusion to support T-cell stemness, TCR removal to reduce GVHD risk, and a high-affinity non-cleavable CD16a to enable antibody-dependent cellular cytotoxicity when a compatible therapeutic antibody is administered.
drug_name
FT825
nct_id_drug_ref
NCT06241456