Near-infrared photoimmunotherapy using antiGD2 antibody for neuroblastoma and osteosarcoma

<h2>ABSTRACT</h2><h3>Introduction</h3> Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer therapy that specifically targets cancer cells. In NIR-PIT, antibody-photo-absorber-conjugates (APCs), specific for cancer antigens, target cancer cells. APCs that bind to antigens and are irradiated with NIR-light kill targeted cells. NIR-PIT has been clinically applied to head and neck squamous cell carcinoma in Japan, but not to pediatric cancers. Generally, neuroblastoma and osteosarcoma express GD2 antigen, making NIR-PIT that targets GD2 an additional treatment option. <h3>Methods</h3> Antihuman GD2 monoclonal antibody (clone 3F8) was conjugated with photo-absorber, IRDye^Ⓡ 700DX. A human neuroblastoma cell (SK-N-SH) was used for <i>in vitro</i> and <i>in vivo</i> experiments, whereas human osteosarcoma cells (NOS-10, MG-63) were utilized for <i>in vitro</i> experiments. Microscopy and flow cytometry was used to evaluate cell death after NIR-PIT, and longitudinal measurement of tumor size and histological observation were utilized to assess the effect of NIR-PIT on the xenograft model. <h3>Results</h3> EthD-1 staining after NIR-PIT confirmed the morphological changes (swelling and bleb formation) observed by microscopy and cell death. Flow cytometry verified the significant increase in dead cells after NIR-PIT. Tumor growth in the mice model was significantly inhibited at day 10 of the experiment and destroyed tumor tissue was histologically observed in the PIT-treated mice. <h3>Conclusion</h3> The efficacy of NIR-PIT with antiGD2 antibody for neuroblastoma and osteosarcoma was indicated. Additionally, NIR-PIT efficacy against neuroblastoma was indicated by the mice model <i>in vivo</i>. Therefore, further experiments and more effective protocols should be considered for clinical application.