CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Bridging transplantation and immunotherapy: Clinical promise of autologous stem cell transplantation with chimeric antigen receptor T-cell therapy.
Bridging transplantation and immunotherapy: Clinical promise of autologous stem cell transplantation with chimeric antigen receptor T-cell therapy.
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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。
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.
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