모달 CAR T 세포: AML에서 TGFβ 매개 면역억제를 극복하기 위한 합성 사이토카인 회로

Key Points

• To develop a synthetic cytokine circuit in CAR T cells to counteract TGFβ-mediated immunosuppression in acute myeloid leukemia.
• Designed a synthetic TGFβ-sensing circuit to express IL-12 and CAR in response to TGFβ.
• Constructs were tested in Jurkat cells and primary T cells with CD70 targeting.
• Evaluated efficacy in vitro on AML cell lines and in vivo with NSG mice models.
• CD70-MODAL12/18 CAR T cells showed reduced baseline IL-12 expression and enhanced cytotoxicity.
• Significant reduction in tumor burden in NSG mice models with ongoing survival analysis.
• Higher frequencies of central memory CD4+ and CD8+ T cells observed with reduced PD-1 expression.