免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Exacerbation of demyelinating polyneuropathy after adoptive cell therapy with tumour-infiltrating lymphocytes by metastatic melanoma.
Exacerbation of demyelinating polyneuropathy after adoptive cell therapy with tumour-infiltrating lymphocytes by metastatic melanoma.
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。
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。
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.
MEMBER ACCOUNT
登录成功会直接打开下一页。