肿瘤细胞治疗研究
英文原题：Targeting Regnase-1 in B7-H3-CAR T cells reprograms the tumor microenvironment and enhances antitumor efficacy for osteosarcoma.
实体瘤微环境是 CAR T 细胞治疗面临的一道免疫抑制性治疗屏障，目前尚不清楚能否通过敲除 CAR T 细胞中的负性调控因子来重塑它。
实体瘤微环境构成 CAR-T 细胞治疗面临的免疫抑制性屏障；目前尚不清楚，敲除 CAR-T 细胞中的负调控因子能否重塑这一微环境。为填补这一认知空白，我们评估了在 B7-H3-CAR-T 细胞中敲除负调控因子 Regnase-1（Reg-1），用于骨肉瘤免疫治疗时产生的细胞内在与外在效应。Reg-1 敲除可增强人源和小鼠源 B7-H3-CAR-T 细胞在体内的抗肿瘤活性。在免疫功能完整的模型中，Reg-1 敲除还使小鼠源 B7-H3-CAR-T 细胞能够营造促炎性微环境，其特征包括产生干扰素-γ（IFN-γ）的内源性 T 细胞和自然杀伤（NK）细胞浸润增加，以及包括 M2 样巨噬细胞在内的抑制性髓系细胞减少。因此，敲除 Reg-1 可带来细胞自主性和非细胞自主性获益，使 Reg-1 敲除的 B7-H3-CAR-T 细胞成为一种有前景的细胞产品，可在实体瘤患者中开展早期临床试验。
The microenvironment in solid tumors represents an immunosuppressive therapeutic barrier to CAR T cell therapy, and it is currently unknown whether it can be reshaped by the deletion of negative regulators in CAR T cells. To address this knowledge gap, we evaluated the intrinsic and extrinsic effects of deleting the negative regulator Regnase-1 (Reg-1) in B7-H3-CAR T cells for the immunotherapy of osteosarcoma. Reg-1 knockout (KO) improved the antitumor activity of human and murine B7-H3-CAR T cells in vivo. In immune-competent models, Reg-1 KO also endowed murine B7-H3-CAR T cells with the ability to create a proinflammatory landscape characterized by an influx of interferon gamma (IFN- )-producing endogenous T cells and natural killer (NK) cells and a reduction of inhibitory myeloid cells, including M2-like macrophages. Thus, deleting Reg-1 has cell- and non-cell-autonomous benefits, nominating Reg-1 KO B7-H3-CAR T cells as a promising cell product for early-phase clinical testing in patients with solid tumors.
MEMBER ACCOUNT
登录成功会直接打开下一页。
