Phase I trial of adoptively transferred tumor-infiltrating lymphocyte immunotherapy following concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma
Phase I trial of adoptively transferred tumor-infiltrating lymphocyte immunotherapy following concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma
复制标题
局部晚期鼻咽癌同步放化疗后过继转移肿瘤浸润淋巴细胞免疫治疗的 I 期试验
DOI：
10.4161/23723556.2014.976507
复制
发表时间：
2015-02-01
期刊：
影响因子：
7.2
通讯作者：
Zeng, Yi-Xin
中科院分区：
文献类型：
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作者：
Li, Jiang;Chen, Qiu-Yan;Zeng, Yi-Xin
利用自体肿瘤浸润淋巴细胞（TIL）进行的癌症诱导细胞疗法（ACT）可在转移性黑色素瘤患者中诱导免疫应答和抗肿瘤活性。在此，我们旨在评估局部晚期鼻咽癌（NPC）患者在同步放化疗（CCRT）后使用扩展TIL的ACT的安全性和抗肿瘤活性。入组了23例新诊断的局部晚期NPC患者，其中20例在CCRT后接受了单剂量的TIL输注。对所有治疗患者的毒性、生存率以及临床和免疫学反应进行了评估。进一步研究了免疫应答和治疗效果之间的相关性。仅观察到轻度不良事件（AE），包括与免疫相关原因一致的3级中性粒细胞减少症（1/23，5%）。20例患者中有19例表现出客观的抗肿瘤反应，18例患者显示无病生存期长于ACT后12个月。14例患者在诊断时检测到可测量的血浆EB病毒（EBV）载量，但在ACT 1周后未发现可测量的EBV载量，17例患者在ACT后6个月仍无法检测到血浆EBV载量。在13例患者中观察到TIL治疗后外周血中EBV抗原特异性T细胞的扩增和持续存在。在4名患者中进一步研究了肿瘤消退与EBV特异性T细胞扩增之间的明显正相关性。该研究表明，NPC患者在CCRT后可以耐受ACT与TIL，并且这种治疗导致持续的抗肿瘤活性和抗EBV免疫应答。一个更大的第二阶段试验正在进行中。
Adoptive cell therapy (ACT) for cancers using autologous tumor-infiltrating lymphocytes (TILs) can induce immune responses and antitumor activity in metastatic melanoma patients. Here, we aimed to assess the safety and antitumor activity of ACT using expanded TILs following concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Twenty-three newly diagnosed, locoregionally advanced NPC patients were enrolled, of whom 20 received a single-dose of TIL infusion following CCRT. All treated patients were assessed for toxicity, survival and clinical and immunologic responses. Correlations between immunological responses and treatment effectiveness were further studied. Only mild adverse events (AEs), including Grade 3 neutropenia (1/23, 5%) consistent with immune-related causes, were observed. Nineteen of 20 patients exhibited an objective antitumor response, and 18 patients displayed disease-free survival longer than 12 mo after ACT. A measurable plasma Epstein–Barr virus (EBV) load was detected in 14 patients at diagnosis, but a measurable EBV load was not found in patients after one week of ACT, and the plasma EBV load remained undetectable in 17 patients at 6 mo after ACT. Expansion and persistence of T cells specific for EBV antigens in peripheral blood following TIL therapy were observed in 13 patients. The apparent positive correlation between tumor regression and the expansion of T cells specific for EBV was further investigated in four patients. This study shows that NPC patients can tolerate ACT with TILs following CCRT and that this treatment results in sustained antitumor activity and anti-EBV immune responses. A larger phase II trial is in progress.