Engineering CAR B cells

We engineer CAR B cells to be activated upon engaging with the tumor antigen in a T-cell-independent manner. The CAR gene, encoded upstream of the antibody, entails a fusion of a Trastuzumab-based scFv to the membranal and signaling domains of either TLR4, promoting T cell independent B cell activation, or CD40, recapitulating T cell dependent B cell activation in the absence of T cells. TLR4-CAR is expected to have the added safety feature of allowing differentiation to short lived plasmablasts only, rather than to LLPCs. Importantly, the endogenous BCR disruption and the redundancy of T cell help make CAR B cells amenable for allogenic application with diminished risk for graft versus host disease (GVHD).