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连接移植与免疫治疗:自体干细胞移植联合 CAR-T 细胞治疗的临床前景

英文原题:Bridging transplantation and immunotherapy: Clinical promise of autologous stem cell transplantation with chimeric antigen receptor T-cell therapy.

查看英文原题

Bridging transplantation and immunotherapy: Clinical promise of autologous stem cell transplantation with chimeric antigen receptor T-cell therapy.

PubMed 2025/08/30(内容时间) Chin J Cancer Res Q1 · IF 6.7(JCR 2025)

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中文摘要

自体干细胞移植(ASCT)和CAR-T 细胞疗法是血液系统恶性肿瘤的重要治疗手段,各有优势和局限。ASCT通过清髓性预处理降低肿瘤负荷,但仍可能复发;CAR-T 可精准靶向恶性细胞,却面临细胞因子释放综合征(CRS)、免疫效应细胞相关神经毒性综合征(ICANS)及持久性有限等挑战。新证据提示,ASCT联合CAR-T 可能产生协同作用:ASCT可重塑免疫微环境、减少免疫抑制细胞并降低CRS风险,而CAR-T 可清除残留病灶并促进免疫恢复。复发/难治性B细胞淋巴瘤和多发性骨髓瘤临床试验显示,完全缓解率(CRR)为72%–100%,2年无进展生存率(PFS)为59%–83%,重度CRS/ICANS发生率低于10%。

然而,协同作用的确切机制、ASCT后CAR-T 输注的最佳时机及理想剂量方案仍需进一步明确。未来研究应优先开展大规模随机对照试验,并建立标准化毒性管理方案,以最大化治疗获益。整合ASCT和CAR-T 的互补优势,是改善高危血液系统恶性肿瘤结局的一种有前景策略;但仍需更多研究验证其疗效并拓展临床适用范围。

展开英文摘要原文

Autologous stem cell transplantation (ASCT) and chimeric antigen receptor T-cell (CAR-T) therapy represent pivotal treatments for hematologic malignancies, each with distinct strengths and limitations. ASCT reduces tumor burden through myeloablative conditioning but remains susceptible to relapse, while CAR-T therapy precisely targets malignant cells but encounters challenges, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and limited persistence.

Emerging evidence suggests that combining ASCT with CAR-T therapy yields synergistic effects. ASCT reshapes the immune microenvironment, lowers immunosuppressive cells and CRS risk, while CAR-T eliminates residual disease and promotes immune recovery. Clinical trials in relapsed/refractory B-cell lymphomas and multiple myeloma demonstrate complete remission rates (CRR) of 72%-100% and two-year progression-free survival (PFS) rates of 59%-83%, with severe CRS/ICANS incidences below 10%.

However, the precise mechanisms underlying this synergy, optimal timing of CAR-T infusion after ASCT, and ideal dosing regimens require further definition. Future research should prioritize large-scale, randomized controlled trials and establish standardized protocols for toxicity management to maximize therapeutic benefits.

By integrating the complementary strengths of ASCT and CAR-T, this combination strategy represents a promising approach for improving outcomes in high-risk hematologic malignancies; however, additional studies are necessary to validate its efficacy and expand its clinical applicability.

论文信息

作者
Yan Y、Dai Z、Li D、Mao X、Huang L
第一作者单位
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.China
通讯作者单位
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China.China
期刊
Chinese journal of cancer research = Chung-kuo yen cheng yen chiu2025 Aug 30
原文标识
PubMed 40979669 · DOI 10.21147/j.issn.1000-9604.2025.04.03