allogeneic hypoimmune B7-H3 CAR T cells

Allogeneic hypoimmune B7-H3 CAR T cells are an investigational "off-the-shelf" cellular immunotherapy designed to treat B7-H3-expressing solid tumors, specifically pancreatic ductal adenocarcinoma (PDAC). The therapy utilizes a hypoimmune (HIP) platform to evade both adaptive and innate immune rejection, allowing for administration without extensive HLA matching. This is achieved through CRISPR-Cas9-mediated disruption of the B2M and CIITA genes to eliminate HLA class I and II expression, and the TRAC gene to prevent graft-versus-host disease (GvHD). Additionally, the cells are engineered to overexpress CD47, which serves as a "don't eat me" signal to inhibit macrophage-mediated phagocytosis and NK cell clearance. The CAR construct incorporates a binder specific to B7-H3 (CD276), an immunomodulatory transmembrane protein that is aberrantly expressed in PDAC and associated with disease progression. Preclinical studies indicate that these HIP-modified CAR T cells retain potent antitumor activity and can effectively control tumor growth in orthotopic PDAC models while remaining protected from host immune detection.

Other names

HIP B7-H3 CAR T cellsallogeneic HIP B7-H3 CAR-T cells