CAR T细胞扩增的幅度与临床功效相关。虽然细胞因子可以增强CAR T细胞增殖，但全身给药的细胞因子可能导致毒性反应。为了在减轻毒性的同时获取细胞因子信号的益处，我们设计了构成活性的合成细胞因子受体嵌合体（构成性涡轮结构域），以一种特异于CAR T细胞的方式进行信号传递。涡轮结构域的模块化设计使单个同源二聚体受体嵌合体产生多样的细胞因子信号输出，并且允许多路复用不同的细胞因子信号。含有IL-2/15Rβ源信号域的涡轮结构域紧密模拟了IL-15的信号传递，并增强了CAR T细胞的效能。靶向BCMA的异基因涡轮CAR T细胞未显示任何异常增殖征象，但展示出增强的扩增能力和抗肿瘤活性，延长了小鼠模型中的存活时间，并防止骨髓外复发。这些结果展示了构成性涡轮结构域实现CAR T细胞的选择性增强的潜力，并证明了异基因BCMA涡轮CAR T细胞的安全性和有效性，支持在多发性骨髓瘤中进行临床评估。

The magnitude of CAR T cell expansion has been associated with clinical efficacy. Although cytokines can augment CAR T cell proliferation, systemically administered cytokines can result in toxicities. To gain the benefits of cytokine signaling while mitigating toxicities, we designed constitutively active synthetic cytokine receptor chimeras (constitutive Turbodomains) that signal in a CAR T cell-specific manner. The modular design of Turbodomains enables diverse cytokine signaling outputs from a single homodimeric receptor chimera and allows multiplexing of different cytokine signals. Turbodomains containing an IL-2/15Rβ-derived signaling domain closely mimicked IL-15 signaling and enhanced CAR T cell potency. Allogeneic TurboCAR T cells targeting BCMA showed no evidence of aberrant proliferation yet displayed enhanced expansion and antitumor activity, prolonging survival and preventing extramedullary relapses in mouse models. These results illustrate the potential of constitutive Turbodomains to achieve selective potentiation of CAR T cells and demonstrate the safety and efficacy of allogeneic BCMA TurboCAR T cells, supporting clinical evaluation in multiple myeloma.