Clin Cancer Res:CMV特异性T细胞治疗胶质母细胞瘤

2020-08-03 MedSci原创 MedSci原创

巨细胞病毒(CMV)抗原在胶质母细胞瘤中存在,但在正常脑组织中不存在,使其成为治疗胶质母细胞瘤的理想的免疫学靶点。

胶质母细胞瘤是星形细胞肿瘤中恶性程度最高的胶质瘤。肿瘤位于皮质下,多数生长于幕上大脑半球各处。呈浸润性生长,常侵犯几个脑叶,并侵犯深部结构,还可经胼胝体波及对侧大脑半球。胶质母细胞瘤生长速度快,70%~80%患者病程在3~6个月,病程超过1年者仅10%。

巨细胞病毒(CMV)抗原在胶质母细胞瘤中存在,但在正常脑组织中不存在,使其成为治疗胶质母细胞瘤的理想的免疫学靶点。

该研究是一项I期的3+3设计的剂量递增(4个剂量水平)型试验。 先收集胶质母细胞瘤患者的高功能自体多克隆CMV pp65特异性T细胞,在体外进行扩增,并经替莫唑胺(100mg/m2)处理3周耗竭非特异性淋巴细胞后输回患者体内。6周一疗程,共4个疗程。

筛选出65例患者,41例巨细胞病毒血清阳性,25例接受白细胞分离,20例至少完成1个疗程的治疗。

未观察到剂量限制性毒性。影像学完全缓解1例,部分缓解2例,中位无进展生存期(PFS)1.3个月[95%CI 0-8.3个月],6个月PFS为19%(95%CI,7%-52%),中位总生存期12个月(95%CI,6个月-未达)。重复输注CMV-T细胞可显著增加循环中CMV-CD8T细胞的数量,但抑制了提示效应活性的细胞因子的产生,尤其是直接来自胶质母细胞瘤的T细胞。

结论:用大剂量替莫唑胺滤除淋巴细胞后的CMV特异性T细胞有良好的耐受性。但显然,CMV血清阳性并不能保证肿瘤对CMV特异性T细胞敏感,提示了CMV抗原表达的异质性。此外,这些T细胞的效应功能有所减弱,表明在进行大规模临床研究之前,需要进一步调控T细胞以防止其功能障碍。

原始出处:

Shiao-Pei Weathers,et al. Glioblastoma-mediated Immune Dysfunction Limits CMV-specific T Cells and Therapeutic Responses: Results from a Phase I/II Trial. Clinical Cancer Research. DOI: 10.1158/1078-0432.CCR-20-0176 Published July 2020

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    2020-08-22 wolongzxh
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  5. 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  6. 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    2020-08-07 147a5a01m24

    666

    0

  7. 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    2020-08-06 chenny

    学习了

    0

  8. 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    2020-08-05 ms3000000449926787

    学习

    0

  9. 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  10. 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    2020-08-04 hdffgjjk

    学习了。

    0

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