Near-infrared photoimmunotherapy (NIR-PIT) on cholangiocarcinoma using a novel catheter device with light emitting diodes.

Near-infrared photoimmunotherapy (NIR-PIT) is a novel therapy for cancers that uses NIR light and antibody-photosensitizer (IR700) conjugates. However, it is difficult to deliver NIR light into the bile duct for cholangiocarcinoma (CCA) from the conventional extracorporeal apparatus. Thus, in this study, we developed a dedicated catheter with light emitting diodes (LEDs) that supersedes conventional external irradiation devices; we investigated the therapeutic effect of NIR-PIT for CCA using the novel catheter. The new catheter was designed to be placed in the bile duct and a temperature sensor was attached to the tip of the catheter to avoid thermal burn. An anti-epidermal growth factor receptor (EGFR) antibody, Panitumumab-IR700 conjugate or anti-human epidermal growth factor receptor type 2 (HER2) antibody, Trastuzumab-IR700 conjugate, was used with EGFR- or HER2-expressing cell lines, respectively. The in vitro efficacy of NIR-PIT was confirmed in cultured cells; the capability of the new catheter for NIR-PIT was then tested in a mouse tumor model. NIR-PIT via the developed catheter treated CCA xenografts in mice. NIR-PIT had an effect in Panitumumab-IR700 conjugate- and Trastuzumab-IR700 conjugate-treated CCA cells that depended on the receptor expression level. Tumor growth was significantly suppressed in mice treated with NIR-PIT using the novel catheter compared with controls (P < .01). NIR-PIT was an effective treatment for EGFR- and HER2-expressing CCA cells, and the novel catheter with mounted LEDs was useful for NIR-PIT of CCA.

Targeting Epidermal Growth Factor Receptor (EGFR) and Human Epidermal Growth Factor Receptor 2 (HER2) Expressing Bladder Cancer Using Combination Photoimmunotherapy (PIT).

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.