DSG3/1-CAART is being designed to target DSG3 and/or DSG1 autoantibodies on pathogenic B cells that cause mcPV.
From a regulatory and clinical trial design perspective, we anticipate many of the elements incorporated into the planned DSG3-CAART trial will carry over to DSG3/1-CAART.
In Vitro Studies
CAAR development for mcPV, based on the targeting of DSG3- and/or DSG1-specific B cells, has shown promising preclinical results. DSG1 CAAR T cells specifically killed DSG1-specific B cells in vitro. In addition, we observed that with a 1:1 mixture of DSG3 and DSG1 CAAR T cells had killing capabilities without synergistic or antagonistic effect.
In Vivo Studies
The activity and toxicity of DSG3 and DSG1-CAAR T cells was evaluated using human skin xenografts in comparison with CART19 cells, which are known from human clinical trials not to cause direct skin toxicity. A 1:1 mixture of DSG3 and DSG1 CAAR T cells did not show off-target toxicity toward human skin in vivo.