Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD - 20892, USA.
Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Sci Rep. 2019 Feb 14;9(1):2084. doi: 10.1038/s41598-019-38575-x.
Bladder cancer (BC) is heterogeneous and expresses various cell surface targets. Photoimmunotherapy (PIT) involves monoclonal antibodies (MAbs) conjugated to a photoabsorber (PA), IR Dye 700Dx, and then activated by near infra-red light (NIR) to specifically target tumors. We have demonstrated that tumors expressing EGFR can be targeted with PIT. However, PIT may be less effective when a tumor lacks "overwhelming" expression of a single target such as EGFR. We present a combinatorial PIT approach for targeting BC expressing EGFR and HER2, using PA- labeled panitumumab (pan) and trastuzumab (tra), respectively. Human BC tissues and cell lines were analyzed for EGFR and HER2 expression. Efficacy of PA-labeled MAbs singly and in combination was analyzed. About 45% of BC tissues stain for both EGFR and HER2. In vitro, the combination of pan IR700 and tra IR700 with NIR was more efficacious than either agent alone. Tumor xenografts treated with combination PIT showed significant tumor growth retardation. Combination PIT is a promising approach for treating BC with low/moderate expression of surface receptors. In addition, given the molecular heterogeneity of bladder cancer, targeting more than one surface receptor may allow for more effective cell death across different bladder tumors.
膀胱癌 (BC) 具有异质性，表达各种细胞表面靶标。光免疫疗法 (PIT) 涉及与光吸收剂 (PA)、IR 染料 700Dx 偶联的单克隆抗体 (MAb)，然后通过近红外光 (NIR) 激活以特异性靶向肿瘤。我们已经证明，表达 EGFR 的肿瘤可以用 PIT 靶向。然而，当肿瘤缺乏 EGFR 等单一靶标的“压倒性”表达时，PIT 可能效果较差。我们提出了一种针对表达 EGFR 和 HER2 的 BC 的组合 PIT 方法，分别使用 PA 标记的 panitumumab (pan) 和 trastuzumab (tra)。分析了人膀胱癌组织和细胞系中 EGFR 和 HER2 的表达。分析了单独和联合使用 PA 标记 MAb 的疗效。约 45%的 BC 组织同时表达 EGFR 和 HER2。体外，pan IR700 和 tra IR700 与 NIR 的联合使用比单独使用任何一种药物都更有效。用组合 PIT 治疗的肿瘤异种移植物显示出明显的肿瘤生长迟缓。组合 PIT 是治疗低/中度表达表面受体的膀胱癌的一种很有前途的方法。此外，鉴于膀胱癌的分子异质性，靶向多个表面受体可能允许在不同的膀胱癌中更有效地诱导细胞死亡。
