Near infrared photoimmunotherapy targeting bladder cancer with a canine anti-epidermal growth factor receptor (EGFR) antibody.
Near infrared photoimmunotherapy targeting bladder cancer with a canine anti-epidermal growth factor receptor (EGFR) antibody.
复制标题
DOI：
10.18632/oncotarget.24876
复制
发表时间：
2018-04-10
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;Okuyama S;Ogata F;Maruoka Y;Knapp DW;Karagiannis SN;Fazekas-Singer J;Choyke PL;LeBlanc AK;Jensen-Jarolim E;Kobayashi H
抗表皮生长因子受体（EGFR）抗体治疗用于EGFR表达的癌症，包括肺癌、结肠癌、头颈癌和膀胱癌，但效果不佳。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，它采用了由NIR光激活的抗体-光吸收剂缀合物。NIR-PIT正在使用西妥昔单抗-IR 700作为缀合物在患有复发性头颈癌的患者中进行临床试验。然而，它的使用仅限于小鼠模型。这是一个努力探索更大的动物模型与NIR-PIT。我们描述了使用重组犬抗EGFR单克隆抗体（mAb），can 225 IgG，共轭的光吸收剂，IR 700DX，在三个EGFR表达犬移行细胞癌（TCC）细胞系作为可能的犬临床研究的前奏。Can 225-IR 700偶联物在体外对EGFR表达细胞进行NIR-PIT后显示出特异性结合和细胞特异性杀伤。在体内研究中，can 225-IR 700偶联物显示了具有高肿瘤背景比的荧光偶联物的蓄积。将携带肿瘤的小鼠分成4组：（1）未处理;（2）仅静脉内注射100 μg can 225-IR 700;（3）仅NIR光暴露;（4）静脉内注射100 μg can 225-IR 700，NIR光暴露。与其他组相比，NIR-PIT治疗显著抑制肿瘤生长（p < 0.001），并且在治疗组中实现了显著延长的存活（p < 0.001相对于其他组）。总之，使用can 225-IR 700的NIR-PIT是一种有希望的治疗犬EGFR表达癌症的方法，包括宠物犬的侵袭性移行细胞癌，可以提供一种翻译到人类的途径。
Anti-epidermal growth factor receptor (EGFR) antibody therapy is used in EGFR expressing cancers including lung, colon, head and neck, and bladder cancers, however results have been modest. Near infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate which is activated by NIR light. NIR-PIT is in clinical trials in patients with recurrent head and neck cancers using cetuximab-IR700 as the conjugate. However, its use has otherwise been restricted to mouse models. This is an effort to explore larger animal models with NIR-PIT. We describe the use of a recombinant canine anti-EGFR monoclonal antibody (mAb), can225IgG, conjugated to the photo-absorber, IR700DX, in three EGFR expressing canine transitional cell carcinoma (TCC) cell lines as a prelude to possible canine clinical studies. Can225-IR700 conjugate showed specific binding and cell-specific killing after NIR-PIT on EGFR expressing cells in vitro. In the in vivo study, can225-IR700 conjugate demonstrated accumulation of the fluorescent conjugate with high tumor-to-background ratio. Tumor-bearing mice were separated into 4 groups: (1) no treatment; (2) 100 µg of can225-IR700 i.v. only; (3) NIR light exposure only; (4) 100 µg of can225-IR700 i.v., NIR light exposure. Tumor growth was significantly inhibited by NIR-PIT treatment compared with the other groups (p < 0.001), and significantly prolonged survival was achieved (p < 0.001 vs. other groups) in the treatment groups. In conclusion, NIR-PIT with can225-IR700 is a promising treatment for canine EGFR-expressing cancers, including invasive transitional cell carcinoma in pet dogs, that could provide a pathway to translation to humans.