Sana生物科技有限公司Sonja Schrepfer课题组的一项最新研究发现了癌症和自身免疫性疾病患者低免疫CD19 CAR T细胞逃避同种异体排斥反应。2025年8月13日出版的《细胞—干细胞》杂志发表了这项成果。

该研究团队报告了对HIP-编辑的CD19 CAR T细胞的ARDENT （NCT05878184）和GLEAM （NCT06294236）试验的探索性免疫分析。尽管存在针对HLA充满的SC291亚群的同种免疫反应，但课题组观察到，在所有患者中，无论剂量或患者的疾病如何，都没有针对完全编辑的HIP CAR T细胞的新生免疫反应。缺乏针对HLA充满的CAR T细胞的抗体被认为是深层组织CD19细胞耗竭的标志，所有60天没有这种抗体的患者外周血中都伴有B细胞耗竭。所提出的免疫数据支持HIP概念避免同种异体排斥反应的可靠性。

据悉，现成的CAR T细胞需要可靠地逃脱同种异体免疫反应，才能成为通用药物。原代T细胞产物SC291通过CD19 CAR、T细胞受体α常数（TRAC）敲除、HLA缺失和CD47过表达的低免疫（HIP）编辑进行工程化。

附：英文原文

Title: Hypoimmune CD19 CAR T cells evade allorejection in patients with cancer and autoimmune disease

Author: Xiaomeng Hu, Pascal Beauchesne, Chenyan Wang, Athena Wong, Tobias Deuse, Sonja Schrepfer

Issue&Volume: 2025-08-13

Abstract: Off-the-shelf CAR T cells need to reliably escape allogeneic immune responses to become universal medicines. The primary T cell product SC291 was engineered with a CD19 CAR, T cell receptor alpha constant (TRAC) knockout, and the hypoimmune (HIP) edits of HLA depletion and CD47 overexpression. Here, we report exploratory immune analyses from the ARDENT (NCT05878184) and GLEAM (NCT06294236) trials with HIP-edited CD19 CAR T cells. Although there was an alloimmune response against HLA-replete subpopulations of SC291, we observed no de novo immune response against fully edited HIP CAR T cells in all patients, irrespective of the dose or the patient’s disease. The lack of antibodies against the HLA-replete CAR T cells was identified as a marker for deep tissue CD19 cell depletion, and all patients without such antibodies for 60 days showed concomitant B cell depletion in peripheral blood. The immune data presented support the reliability of the HIP concept to evade allorejection.

DOI: 10.1016/j.stem.2025.07.009

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00266-8