Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892-1088, USA.
Bioconjug Chem. 2012 Mar 21;23(3):604-9. doi: 10.1021/bc200648m. Epub 2012 Mar 8.
Armed antibody-based targeted molecular therapies offer the possibility of effective tumor control with a minimum of side effects. Photoimmunotherapy (PIT) employs a monoclonal antibody-phototoxic phthalocyanine dye, IR700 conjugate, that is activated by focal near-infrared (NIR) light irradiation after antibody binding to the targeted tumor cell surface leading to rapid necrotic cell death. Therapy by single NIR light irradiation was effective without significant side effects; however, recurrences were seen in most treated mice probably because of inhomogeneous distribution of panitumumab-IR700 immunoconjugate in the tumor, leading to ineffective PIT. We describe here an optimized regimen of effective PIT method for the same HER1-overexpressing tumor model (A431) with fractionated administration of panitumumab-IR700 conjugate followed by systematic repeated NIR light irradiation to the tumor based on timing of antibody redistribution into the remnant tumor under the guidance of IR700 fluorescence signal. Eighty percent of the A431 tumors were eradicated with repeated PIT without apparent side effects and survived tumor-free for more than 120 days even after stopping therapy at day 30. Therapeutic effects were monitored using IR700 fluorescent signal. PIT is a promising highly selective and clinically feasible theranostic method for treatment of mAb-binding tumors with minimal off-target effects.
基于抗体的靶向分子治疗为有效控制肿瘤提供了可能，同时副作用最小。光免疫疗法（PIT）采用单克隆抗体-光毒性酞菁染料 IR700 缀合物，在与靶肿瘤细胞表面结合后，用焦点近红外（NIR）光照射激活，导致快速坏死细胞死亡。单次 NIR 光照射治疗有效，无明显副作用；然而，大多数治疗小鼠出现复发，可能是由于 panitumumab-IR700 免疫偶联物在肿瘤中的不均匀分布，导致 PIT 无效。我们在此描述了一种针对相同 HER1 过表达肿瘤模型（A431）的优化 PIT 方法，即 panitumumab-IR700 缀合物的分次给药，然后根据 IR700 荧光信号引导下抗体重新分布到残余肿瘤中的时间，对肿瘤进行系统的重复 NIR 光照射。80%的 A431 肿瘤在重复 PIT 后被根除，没有明显的副作用，即使在第 30 天停止治疗后，也能无瘤存活超过 120 天。使用 IR700 荧光信号监测治疗效果。PIT 是一种有前途的高度选择性和临床可行的治疗方法，用于治疗 mAb 结合肿瘤，副作用最小。
