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转移性黑色素瘤所致脱髓鞘性多神经病在 TIL(肿瘤浸润淋巴细胞)过继细胞治疗后加重

英文原题:Exacerbation of demyelinating polyneuropathy after adoptive cell therapy with tumour-infiltrating lymphocytes by metastatic melanoma.

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Exacerbation of demyelinating polyneuropathy after adoptive cell therapy with tumour-infiltrating lymphocytes by metastatic melanoma.

PubMed 2025/08/21(内容时间) Swiss Med Wkly Q2 · IF 1.6(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

采用TIL(肿瘤浸润淋巴细胞)的过继细胞疗法(ACT)是一种有效的个体化免疫治疗,适用于经多线治疗的晚期黑色素瘤患者。TIL-ACT通过切除肿瘤样本扩增肿瘤特异性T细胞,并在细胞培养中用白细胞介素2(IL-2)刺激。随后,患者接受环磷酰胺和氟达拉滨非清髓性淋巴细胞清除化疗,再回输自体TIL。之后通过给予大剂量IL-2,支持患者体内TIL活化。尽管TIL-ACT有效,仍需进一步提升疗效并降低毒性。这一多步骤复杂治疗方案的多数毒性来自预处理化疗和大剂量IL-2治疗。巴塞尔大学医院目前在一项进行中的I期试验(BaseTIL-03M)中评估一种实验性TIL-ACT方案:以ANV419替代大剂量IL-2,在体内激活TIL。ANV419是一种新型抗体-细胞因子融合蛋白,由IL-2与抗IL-2单克隆抗体融合构成。

该研究主要终点为安全性。本文报告一名纳入BaseTIL-03M试验、患有慢性炎性脱髓鞘性多发性神经病的患者接受ANV419联合TIL-ACT后发生急性多发性神经病的病例,临床诊断为格林-巴利综合征。

展开英文摘要原文

Adoptive cell therapy (ACT) with tumour-infiltrating lymphocytes (TIL) is an effective personalised immunotherapy for patients with advanced pretreated melanoma. For TIL-ACT, tumour-specific T cells are expanded from excised tumour samples and stimulated in cell culture with interleukin-2 (IL-2). The resulting autologous tumour-infiltrating lymphocytes are reinfused to the patient after a non-myeloablative lymphodepleting chemotherapy with cyclophosphamide and fludarabine. Thereafter, activation of tumour-infiltrating lymphocytes in the patient is supported by the administration of high-dose IL-2.

Although effective, there is a need for enhancement of TIL-ACT in terms of effectiveness and toxicity. Most of the toxicity in this multistep, complex treatment regimen is due to the preparative chemotherapy and high-dose IL-2 treatment.

At University Hospital Basel, we are currently evaluating an experimental approach of TIL-ACT in which we replace high-dose IL-2 by in vivo tumour-infiltrating lymphocyte activation with ANV419, a novel antibody-cytokine fusion protein consisting of IL-2 fused to an anti-IL-2 monoclonal antibody, in an ongoing phase I trial (BaseTIL-03M). The primary endpoint of the study is safety.

We herein describe the case of a patient included in the BaseTIL-03M trial with chronic inflammatory demyelinating polyneuropathy who received TIL-ACT with ANV419 and developed an acute polyneuropathy of Guillain-Barr syndrome.

论文信息

作者
Canini E、Pacchin L、Blackham AK、Lorscheider J、Passweg J、Zippelius A、Läubli H、Mutke MR
第一作者单位
Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.Switzerland
通讯作者单位
Innovation Focus Cell Therapies, University Hospital Basel, Basel, Switzerland.Switzerland
文献类型
病例报告 · 非美国政府资助研究
期刊
Swiss medical weekly2025 Aug 21
原文标识
PubMed 41085476 · DOI 10.57187/s.4221