Introduction

This invention concerns the creation of powerful CAR T cells for treating CD19+, CD20+ or CD22+ tumors, such as leukaemia and lymphoid malignancies, which provide increased safety for the treatment of said tumors and prevent epitope masking in CAR+ B-cell leukaemia blasts. Such CAR T cells can decrease the potential risk of CD19-/CAR+, CD20-/CAR+ or CD22-/CAR+ leukemic relapse.

Technical features

CAR T-cell therapy induces a rapid and sustained clinical response, but several factors can jeopardize the efficacy and safety of such treatment, such as the risk of relapse, cytokine release syndrome (CRS), and on-target off-tumor effect. This invention suggests the use of constructs designed to eliminate or minimize the side effects described, as confirmed by in vitro and in vivo tests. In particular, the use of a VL-VH short linker and the introduction of the inducible caspase 9 suicide gene allow respectively to regulate the proliferation of unwanted CAR T cells and to reduce the effect of autoimmune toxicity.

Possible Applications

• Treatment of CD19+, CD20+ or CD22+ tumors
• Personalized treatment

Advantages

• Increased efficacy and safety of CAR T cell therapy
• Control of CAR+ leukemic cells both in vitro and in vivo
• Possible increase in patients eligible for the treatment