Near infrared photoimmunotherapy of B-cell lymphoma
Near infrared photoimmunotherapy of B-cell lymphoma
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DOI：
10.1016/j.molonc.2016.07.010
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发表时间：
2016-11-01
影响因子：
6.6
通讯作者：
Kobayashi, Hisataka
中科院分区：
文献类型：
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作者：
Nagaya, Tadanobu;Nakamura, Yuko;Kobayashi, Hisataka
近红外光免疫疗法（NIR-PIT）是一种新型的、高选择性的癌症治疗诊断学，它采用抗体-光吸收剂缀合物（APC）。NIR-PIT已经成功地用APC治疗了临床前肿瘤模型，目前正在进行针对EGFR的头颈癌患者的首次人体I期临床试验。CD 20在许多B细胞淋巴瘤中高度表达，并且正在成为这种疾病的分子靶点。在这里，我们描述了使用抗CD 20单克隆抗体（mAb），利妥昔单抗-IR 700 APC在两个CD 20表达淋巴瘤小鼠模型的B细胞淋巴瘤的NIR-PIT。本研究中使用表达CD 20的B细胞淋巴瘤细胞系（Daudi和拉莫斯）。利妥昔单抗-IR 700，与IRDye 700DX结合的利妥昔单抗，仅在体外暴露于NIR光后才显示特异性结合和细胞特异性杀伤。为了评估NIR-PIT在体内的作用，将荷瘤小鼠分成4组：（1）对照;（2）仅APC静脉内;（3）仅NIR光暴露;（4）APC和NIR光（NIR-PIT）。每周进行这些检查，最多持续3周。Rituximab-IR 700在体内显示出高肿瘤蓄积和高靶向背景比。与其他组相比，NIR-PIT显着抑制了肿瘤生长（两种肿瘤的p < 0.001），并且两种肿瘤的生存期显着延长（与其他组相比，Daudi肿瘤的p < 0.001，拉莫斯肿瘤的p < 0.0001）。超过一半的肿瘤用这种单一的NIR-PIT方案治愈。总之，抗CD 20利妥昔单抗-IR 700作为针对B细胞淋巴瘤的NIR-PIT的高效APC起作用。由Elsevier B. V.代表欧洲生物化学学会联合会出版。
Near infrared photoimmunotherapy (NIR-PIT) is a new, highly-selective cancer theranostics that employs an antibody-photo absorber conjugate (APC). NIR-PIT has successfully treated preclinical tumor models with APCs and is now in the first-in-human phase 1 clinical trial for head and neck cancer patients against EGFR. CD20 is highly expressed in many B-cell lymphomas and is emerging as a molecular target for this disease. Here, we describe the use of the anti-CD20 monoclonal antibody (mAb), rituximab-IR700 APC for NIR-PIT of B-cell lymphoma in two CD20-expressing lymphoma mouse models. CD20 expressing B-cell lymphoma cell lines (Daudi and Ramos) were used in this study. Rituximab-IR700, rituximab conjugated with IRDye700DX, showed specific binding, and cell-specific killing only after exposure of NIR light to both cells in vitro. To evaluate effects of NIR-PIT in vivo, tumor-bearing mice were separated into 4 groups: (1) control; (2) APC i.v. only; (3) NIR light exposure only; (4) APC and NIR light (NIR-PIT). These were performed every week for up to 3 weeks. Rituximab-IR700 showed high tumor accumulation and high target-to-background ratio in vivo. Tumor growth was significantly inhibited by NIR-PIT in comparison with the other groups ( p < 0.001 for both tumors), and survival was significantly prolonged in both tumors ( p < 0.001 for Daudi tumors and p < 0.0001 for Ramos tumors vs other groups). More than half of tumors were cured with this single regimen of NIR-PIT. In conclusion, anti-CD20 rituximab-IR700 works as a highly effective APC for NIR-PIT against B-cell lymphoma. Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies.