不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel：ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
干细胞记忆型 EBV 特异性 T 细胞控制 EBV 肿瘤生长并在体内持续存在
英文原题：Stem cell memory EBV-specific T cells control EBV tumor growth and persist in vivo.
查看英文原题
Stem cell memory EBV-specific T cells control EBV tumor growth and persist in vivo.
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中文摘要
过继性T细胞治疗（ACT），即将明确的T细胞免疫治疗性转移给患者，在对抗包括难治性病毒感染在内的多种人类疾病方面具有巨大潜力，但细胞的持久性和长期存活仍是令人担忧的问题。极早期分化的干细胞记忆T细胞（T SCMs）具有优越的自我更新、植入、持久性和抗癌疗效，但其在抗病毒ACT中的潜力仍不清楚。在此，我们开发了一种临床可扩展的方案，用于扩增EBV特异性T SCM富集T细胞，这些细胞具有高比例的CD4+ T细胞和广泛的EBV抗原覆盖。这些细胞在EBV诱导的淋巴瘤异种移植模型中显示出肿瘤控制，并且在肿瘤浸润、体内增殖、持久性、功能性CD4+ T细胞比例以及EBV抗原特异性多样性方面优于先前的ACT方案。因此，我们的方案可能为针对EBV相关疾病（包括肿瘤）及其他适应症的下一代强效未修饰抗原特异性细胞疗法铺平道路。
展开英文摘要原文
Adoptive T cell therapy (ACT), the therapeutic transfer of defined T cell immunity to patients, offers great potential in the fight against different human diseases including difficult-to-treat viral infections, but persistence and longevity of the cells are areas of concern. Very-early-differentiated stem cell memory T cells (T SCMs ) have superior self-renewal, engraftment, persistence, and anticancer efficacy, but their potential for antiviral ACT remains unknown.
Here, we developed a clinically scalable protocol for expanding Epstein-Barr virus (EBV)-specific T SCM -enriched T cells with high proportions of CD4 + T cells and broad EBV antigen coverage. These cells showed tumor control in a xenograft model of EBV-induced lymphoma and were superior to previous ACT protocols in terms of tumor infiltration, in vivo proliferation, persistence, proportion of functional CD4 + T cells, and diversity of EBV antigen specificity.
Thus, our protocol may pave the way for the next generation of potent unmodified antigen-specific cell therapies for EBV-associated diseases, including tumors, and other indications.
论文信息
- 作者
- Palianina D、Mietz J、Stühler C、Arnold B、Bantug G、Münz C、Chijioke O、Khanna N
- 单位
- Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland.Switzerland
- 文献类型
- 非美国政府资助研究
- 期刊
- Science advances2024 Aug 23
- 原文标识
- PubMed 39178248 · DOI 10.1126/sciadv.ado2048
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