重编程工程化自体 T 细胞以克服 Merkel 细胞癌患者的耐药性
Reprogramming engineered autologous T cells to overcome resistance in patients with Merkel cell carcinoma.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
晚期癌症中的自体工程化 T 细胞受体治疗
英文原题：Autologous engineered T cell receptor therapy in advanced cancer.
查看英文原题
Autologous engineered T cell receptor therapy in advanced cancer.
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中文摘要
为克服过继性细胞治疗（ACT）相关的挑战，我们开发了一项个性化自体T细胞治疗项目。具有HLA-A*02:01等位基因且肿瘤表达PRAME、MAGEA1、MAGEA4、MAGEA8、NY-ESO-1、COL6A3外显子6、MXRA5和/或MMP1的晚期癌症患者接受白细胞分离术和T细胞产品制备。患者接受淋巴细胞清除、IMA101输注以及白细胞介素2治疗14天。在214例筛选患者中，14例接受治疗（6例，IMA101；8例，IMA101联合atezolizumab）。最常见的不良事件为细胞因子释放综合征（G1，n=6；G2，n=4）和血细胞减少。在第6周时，12例（85.7%）患者疾病稳定。3例患者分别获得12.9、7.3和13.7个月的持续疾病稳定。中位无进展生存期和总生存期分别为3.4个月和9.4个月。靶向特异性T细胞扩增，最高占CD8+细胞的78.7%。
总之，IMA101可行且耐受性良好，发挥了多靶点ACT的潜力，值得进一步研究。
展开英文摘要原文
To overcome challenges associated with adoptive cell therapy (ACT), we developed a personalized autologous T-cell therapy program. Patients with advanced cancer with HLA-A *02:01 allele and tumor expression of PRAME, MAGEA1, MAGEA4, MAGEA8, NY-ESO-1, COL6A3 exon 6, MXRA5, and/or MMP1 underwent leukapheresis and T-cell product manufacturing. Patients received lymphodepletion, IMA101 infusion and interleukin 2 for 14 days. Of 214 screened patients, 14 were treated (6, IMA101; 8, IMA101 and atezolizumab).
The most common adverse events were cytokine release syndrome (G1, n = 6; G2, n = 4) and cytopenia. At 6 weeks, 12 (85. 7%) patients had stable disease. Three patients had prolonged disease stabilization for 12. 9, 7. 3, and 13. 7 months, respectively. The median progression-free survival and overall survival were 3. 4 months and 9. 4 months, respectively. Target-specific T cells expanded to constitute up to 78. 7% of CD8+ cells.
In conclusion, IMA101 was feasible and well tolerated, leveraging the potential of multi-targeted ACT that warrants further investigation.
论文信息
- 作者
- Tsimberidou AM、Baysal MA、Chakraborty A、Andersson BS
- 第一作者单位
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.United States
- 通讯作者单位
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.United States
- 文献类型
- 综述 · 非美国政府资助研究 · 美国 NIH 资助研究
- 期刊
- Human vaccines & immunotherapeutics2023 Dec 15
- 原文标识
- PubMed 38114231 · DOI 10.1080/21645515.2023.2290356
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