Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Eureka Therapeutics, Inc., Emeryville, CA, USA.
J Cancer Res Clin Oncol. 2023 Jul;149(7):2757-2769. doi: 10.1007/s00432-022-04132-9. Epub 2022 Jul 1.
A barrier to widespread adoption of chimeric antigen receptor (CAR) T-cell therapy is toxicity. To address this, we recently developed a novel antibody-T-cell receptor (AbTCR) platform (trademarked as ARTEMIS) which was designed to leverage natural immune receptor signaling and regulation. The AbTCR platform includes a gamma/delta (γδ) TCR-based AbTCR construct and a separate co-stimulatory molecule, both engineered to be tumor-specific. Here, we aim to assess the safety and preliminary efficacy of a CD19-directed AbTCR T-cell therapy.
We generated ET019003 T cells, which are autologous CD19-directed AbTCR T cells. We then conducted an early phase I study to evaluate the safety and preliminary efficacy of ET019003 T cells for the treatment of CD19-positive relapsed/refractory (r/r) B-cell lymphoma.
Sixteen patients enrolled in this study and 12 patients were treated. Of the 12 patients treated, 6 patients (50%) achieved a complete response (CR), and 4 (33%) achieved a partial response (PR) (best objective response rate [ORR] of 83%). CRs were durable, including 2 patients with ongoing CRs for 22.7 months and 23.2 months. ET019003 was well-tolerated with an attractive safety profile. No patients experienced severe (grade ≥ 3) cytokine release syndrome (CRS) and only 1 patient experienced immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade. Significant elevations of cytokine levels were not seen, even in patients with marked expansion of ET019003 T cells.
This study provides initial clinical validation of the AbTCR platform as a novel cancer treatment with the potential to provide durable clinical benefit with low toxicity.
NCT03642496; Date of registration: August 22, 2018.
嵌合抗原受体 (CAR) T 细胞疗法广泛应用的一个障碍是毒性。为了解决这个问题，我们最近开发了一种新型抗体 - T 细胞受体 (AbTCR) 平台（商标为 ARTEMIS），旨在利用天然免疫受体信号和调节。AbTCR 平台包括基于 γ/δ (γδ) TCR 的 AbTCR 构建体和另一个单独的共刺激分子，两者均被设计为肿瘤特异性。在这里，我们旨在评估 CD19 定向 AbTCR T 细胞治疗的安全性和初步疗效。
我们生成了 ET019003 T 细胞，这是一种自体 CD19 定向 AbTCR T 细胞。然后，我们进行了一项早期的 I 期研究，以评估 ET019003 T 细胞治疗 CD19 阳性复发/难治性 (r/r) B 细胞淋巴瘤的安全性和初步疗效。
这项研究共纳入了 16 名患者，其中 12 名患者接受了治疗。在接受治疗的 12 名患者中，6 名患者（50%）达到了完全缓解 (CR)，4 名患者（33%）达到了部分缓解 (PR)（最佳客观缓解率 [ORR]为 83%）。CR 是持久的，包括 2 名患者的持续 CR 时间分别为 22.7 个月和 23.2 个月。ET019003 具有良好的耐受性和有吸引力的安全性特征。没有患者出现严重（等级≥3）细胞因子释放综合征 (CRS)，只有 1 名患者出现任何等级的免疫效应细胞相关神经毒性综合征 (ICANS)。即使在 ET019003 T 细胞明显扩增的患者中，也没有观察到细胞因子水平的显著升高。
这项研究初步验证了 AbTCR 平台作为一种新型癌症治疗方法的临床应用，具有提供持久临床获益和低毒性的潜力。
NCT03642496；注册日期：2018 年 8 月 22 日。
