In immunodeficient mice, anti-CD3ε PEBL-T cells had markedly reduced GVHD potential; when transduced with anti-CD19 CAR, these T cells killed engrafted leukemic cells.
We demonstrate that alloreactive T cells expressing CD28-costimulated CD19 CARs experience enhanced stimulation, resulting in the progressive loss of both their effector function and proliferative potential, clonal deletion, and significantly decreased occurrence of GVHD.
CD5(+)CD19(+) B cell, CD5(+)CD43(+)CD19(+) B cell, and CD27(+)CD43(+) B cell counts were significantly lower in the patients with previous chronic GVHD, and this effect of GVHD was similar in both CD5(+) and CD5(-) within the CD27(+)CD43(+) B cell subset.