Near infrared photoimmunotherapy with an anti-mesothelin antibody.
Near infrared photoimmunotherapy with an anti-mesothelin antibody.
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DOI：
10.18632/oncotarget.8025
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发表时间：
2016-04-26
期刊：
影响因子：
--
通讯作者：
Kobayashi H
中科院分区：
文献类型：
--
作者：
Nagaya T;Nakamura Y;Sato K;Zhang YF;Ni M;Choyke PL;Ho M;Kobayashi H
近红外光免疫疗法（NIR-PIT）是一种采用抗体-光子吸收偶联物（APC）的新型高选择性肿瘤治疗方法。当APC附着在其靶细胞上并暴露在近红外光下时，观察到高度选择性的细胞杀伤。NIR-PIT已被证明具有有限数量的抗体。间皮素在几种恶性肿瘤中过度表达，并正在成为一种治疗靶点。最近产生了一种针对间皮素的人源化抗体（hYP218），显示出高亲和力结合。在这里，我们描述了NIR-PIT的功效，使用hYP218作为APC内的抗体来靶向表达A431/H9的间皮素细胞。将hYP218抗体偶联到光吸收剂IR700上，与细胞一起孵育。hYP218-IR700与细胞特异性结合，并在体外观察到细胞特异性杀伤。在胸腺裸鼠体内植入A431/H9细胞后，对荷瘤小鼠进行NIR-PIT治疗；注射后第1天给予50 J/cm2的近红外光照，第2天给予100 J/cm2的近红外光照。hYP218-IR700表现出高肿瘤积累和高肿瘤背景比（TBR）。与其他对照组相比，NIR-PIT治疗显著抑制肿瘤生长（p < 0.001），显著延长生存期（p < 0.0001）。因此，新的抗间皮素抗体hYP218适合作为NIR-PIT的抗体-药物偶联物。此外，带有hYP218-IR700的NIR-PIT是治疗表达间皮素的肿瘤的有希望的候选者，可以很容易地转化为人类。
Near Infrared-Photoimmunotherapy (NIR-PIT) is a new, highly selective tumor treatment that employs an antibody-photon absorber conjugate (APC). When the APC attaches to its target cell and is exposed to NIR light, highly selective cell killing is observed. NIR-PIT has been demonstrated with a limited number of antibodies. Mesothelin is overexpressed in several malignancies and is emerging as a therapeutic target. A recently humanized antibody (hYP218) has been generated against mesothelin that demonstrates high affinity binding. Here, we describe the efficacy of NIR-PIT, using hYP218 as the antibody within the APC to target a mesothelin expressing A431/H9 cell. The hYP218 antibody was conjugated to a photo-absorber, IR700 and incubated with the cells. The hYP218-IR700 showed specific binding to cells and cell-specific killing was observed in vitro. After implanting A431/H9 cells in an athymic nude mouse, tumor-bearing mice were treated with the following regimen of NIR-PIT; 100 μg of hYP218-IR700 i.v., NIR light was administered at 50 J/cm2 on day 1 after injection and 100 J/cm2 of light on day 2 after injection. The hYP218-IR700 showed high tumor accumulation and a high tumor-background ratio (TBR). Tumor growth was significantly inhibited by NIR-PIT treatment compared with the other control groups (p < 0.001), and significantly prolonged survival (p < 0.0001 vs other groups). Thus, the new anti-mesothelin antibody, hYP218, is suitable as an antibody-drug conjugate for NIR-PIT. Furthermore, NIR-PIT with hYP218-IR700 is a promising candidate for the treatment of mesothelin-expressing tumors that could be readily translated to humans.
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