Near-Infrared Photoimmunotherapy Targeting Prostate Cancer with Prostate-Specific Membrane Antigen (PSMA) Antibody.
Near-Infrared Photoimmunotherapy Targeting Prostate Cancer with Prostate-Specific Membrane Antigen (PSMA) Antibody.
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DOI：
10.1158/1541-7786.mcr-17-0164
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发表时间：
2017-09
期刊：
影响因子：
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通讯作者：
Kobayashi H
中科院分区：
文献类型：
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作者：
Nagaya T;Nakamura Y;Okuyama S;Ogata F;Maruoka Y;Choyke PL;Kobayashi H
前列腺特异性膜抗原（PSMA）是一种膜蛋白，在前列腺癌中过度表达，为分子治疗提供了一个有吸引力的靶点。近红外光免疫疗法（NIR-PIT）是一种高度选择性的肿瘤治疗方法，采用抗体-光吸收剂缀合物（APC）。在这里，我们描述了 NIR-PIT 的功效，使用与光吸收剂 IR700DX 缀合的全人 IgG1 抗 PSMA 单克隆抗体 (mAb)，在表达 PSMA 的 PC3 前列腺癌细胞系中。抗 PSMA-IR700 显示出特异性结合，并在体外将细胞暴露于 NIR 后观察到细胞特异性杀伤。在体内研究中，抗PSMA-IR700表现出高肿瘤积累和高肿瘤背景比。荷瘤小鼠被分为4组：(1)不治疗； (2) 100 μg 抗 PSMA-IR700 静脉注射； (3)近红外光照射； (4) 静脉注射 100 μg 抗 PSMA-IR700，进行近红外光照射。这些每周进行一次，持续长达 3 周。与其他对照组相比，NIR-PIT 治疗显着抑制了肿瘤生长（p < 0.001），并且显着延长了生存期（与其他对照组相比，p < 0.0001）。 NIR-PIT 治愈了超过三分之二的肿瘤。总之，抗 PSMA 抗体适合作为 NIR-PIT 的 APC。此外，带有抗 PSMA-IR700 抗体的 NIR-PIT 是治疗表达 PSMA 的肿瘤的有希望的候选者，并且可以很容易地转化为人类。
Prostate-specific membrane antigen (PSMA) is a membrane protein that is overexpressed manifold in prostate cancer and provides an attractive target for molecular therapy. Near infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate (APC). Here, we describe the efficacy of NIR-PIT, using a fully human IgG1 anti-PSMA monoclonal antibody (mAb), conjugated to the photo-absorber, IR700DX, in a PSMA expressing PC3 prostate cancer cell line. Anti-PSMA-IR700 showed specific binding and cell-specific killing was observed after exposure of the cells to NIR in vitro. In the in vivo study, anti-PSMA-IR700 showed high tumor accumulation and high tumor-background ratio. Tumor-bearing mice were separated into 4 groups: (1) no treatment; (2) 100 μg of anti-PSMA-IR700 i.v.; (3) NIR light exposure; (4) 100 μg of anti-PSMA-IR700 i.v., NIR light exposure was administered. These were performed every week for up to 3 weeks. Tumor growth was significantly inhibited by NIR-PIT treatment compared with the other control groups (p < 0.001), and significantly prolonged survival was achieved (p < 0.0001 vs other control groups). More than two thirds of tumors were cured with NIR-PIT. In conclusion, the anti-PSMA antibody is suitable as an APC for NIR-PIT. Furthermore, NIR-PIT with the anti-PSMA-IR700 antibody is a promising candidate of the treatment of PSMA-expressing tumors and could be readily translated to humans.