Blocking PTPN2 improves human CAR T cell cancer-fighting ability and long-term memory in mouse models

Targeting PTPN2 in CAR T cells significantly enhanced their effectiveness against solid tumors.

• Inhibition or deletion of PTPN2 improved CAR and cytokine signaling in anti-LeY CAR T cells.
• This targeting led to increased expansion, activation, and cytotoxicity of CAR T cells both in vitro and in vivo.
• PTPN2-deficient CAR T cells were more effective in suppressing the growth of human tumor xenografts in mice compared to unedited CAR T cells.
• Enhanced tumor repression was also observed with the use of a small-molecule inhibitor of PTPN2.
• Analysis indicated that PTPN2 deficiency resulted in a higher generation of CAR T cells with long-lived memory characteristics and increased persistence within tumors.

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