嵌合抗原受体 (CAR)-T 细胞可以有效治疗白血病，但持续的抗肿瘤反应可能会因缺乏 CAR-T 细胞持久性而受到阻碍。细胞毒性效应T细胞的寿命很短，建立具有记忆功能的CAR-T细胞以确保免疫监视非常重要。记忆 T 细胞依赖于细胞因子的支持，其中 IL7 受体的 IL7 激活至关重要。然而，IL7 受体表面表达受到 IL7 暴露的负调节。我们的目标是通过为 CAR-T 细胞配备持续的 IL7Rα 信号来支持 CAR-T 的持久性。我们对 T 细胞进行了工程改造，使其持续分泌 IL7 或表达抗 AML 靶向的 IL7Rα 嵌合细胞因子受体 (CCR)，并表征了这些细胞类型的表型。随着 IL7R 的激活，CCR-T 细胞中的典型下游信号传导被激活。当与细胞毒性 CAR 共表达时，CCR 和 CAR 的功能得以保留。我们设计了混合 CAR-CCR，并注意到细胞内结构域的膜邻近性对于信号传导至关重要。这些数据表明，可以通过 IL7Rα 结构域的表达来提供具有规范信号传导和功能的细胞内在细胞因子支持，无论是独立表达还是整合到用于抗癌治疗的细胞毒性 CAR 中。

Chimeric Antigen Receptor (CAR)-T cells can effectively treat leukemias, but sustained anti-tumor responses can be hindered by a lack of CAR-T cell persistence. Cytotoxic effector T cells are short-lived, and establishment of CAR-T cells with memory to ensure immune surveillance is important. Memory T cells depend on cytokine support, with IL7 activation of the IL7 receptor being critical. However, IL7 receptor surface expression is negatively regulated by exposure to IL7. We aimed to support CAR-T persistence by equipping CAR-T cells with a sustained IL7Rα signal. We engineered T cells to constitutively secrete IL7 or to express an anti-AML-targeted IL7Rα-Chimeric Cytokine Receptor (CCR) and characterized the phenotype of these cell types. Canonical downstream signaling was activated in CCR-T cells with IL7R activation. When co-expressed with a cytotoxic CAR, functionality of both the CCR and CAR was maintained. We designed hybrid CAR-CCRs and note membrane proximity of the intracellular domains as vital for signaling. These data show cell-intrinsic cytokine support with canonical signaling and functionality can be provided via expression of an IL7Rα-domain whether independently expressed or incorporated into a cytotoxic CAR for use in anti-cancer therapy.