Development of a new minimally invasive phototherapy for lung cancer using antibody–toxin conjugate

Abstract

Abstract Background Photodynamic therapy (PDT) is a cancer‐targeted treatment that uses a photosensitizer (PS) and laser irradiation. The effectiveness of current PDT using red light for advanced cancers is limited, because red light can only reach depths within a few millimeters. To enhance the antitumor effect for lung cancers, we developed a new phototherapy, intelligent targeted antibody phototherapy (iTAP). This treatment uses a combination of immunotoxin and a PS, mono‐L‐aspartyl chlorin e6 (NPe6). Methods We examined whether cetuximab encapsulated in endosomes was released into the cytosol by PS in PDT under light irradiation. A431 cells were treated with fluorescein isothiocyanate‐labeled cetuximab, NPe6, and light irradiation and were observed with fluorescence microscopy. We analyzed the cytotoxicity of saporin‐conjugated cetuximab (IT‐cetuximab) in A431, A549, and MCF7 cells and the antitumor effect in model A549‐bearing mice in vivo using the iTAP method. Results Fluorescent microscopy analysis showed that the photodynamic effect of NPe6 (20 μM) and light irradiation (37.6 J/cm2) caused the release of cetuximab from the endosome into the cytosol. In vitro analysis demonstrated that the iTAP method enhanced the cytotoxicity of IT‐cetuximab by the photodynamic effect. In in vivo experiments, compared with IT‐cetuximab alone or PDT alone, the iTAP method using a low dose of IT‐cetuximab showed the greatest enhancement of the antitumor effect. Conclusions Our study is the first report of the iTAP method using NPe6 for lung cancer cells. The iTAP method may become a new, minimally invasive treatment superior to current PDT methods.

Keywords

• drug delivery system
• endosomal escape
• immunotoxin
• mono‐l‐aspartyl chlorin e6 (NPe6)
• photodynamic therapy