Disialoganglioside GD2-Targeted Near-Infrared Photoimmunotherapy (NIR-PIT) in Tumors of Neuroectodermal Origin.
Fuyuki F InagakiTakuya KatoAki FurusawaRyuhei OkadaHiroaki WakiyamaHideyuki FurumotoShuhei OkuyamaPeter C BlackHisataka KobayashiPublished in: Pharmaceutics (2022)
Disialoganglioside (GD2) is a subtype of glycolipids that is highly expressed in tumors of neuroectodermal origins, such as neuroblastoma and osteosarcoma. Its limited expression in normal tissues makes GD2 a potential target for precision therapy. Several anti-GD2 monoclonal antibodies are currently in clinical use and have had moderate success. Near-infrared photoimmunotherapy (NIR-PIT) is a cancer therapy that arms antibodies with IRDye700DX (IR700) and then exposes this antibody-dye conjugate (ADC) to NIR light at a wavelength of 690 nm. NIR light irradiation induces a profound photochemical response in IR700, resulting in protein aggregates that lead to cell membrane damage and death. In this study, we examined the feasibility of GD2-targeted NIR-PIT. Although GD2, like other glycolipids, is only located in the outer leaflet of the cell membrane, the aggregates formation exerted sufficient physical force to disrupt the cell membrane and kill target cells in vitro. In in vivo studies, tumor growth was significantly inhibited after GD2-targeted NIR-PIT, resulting in prolonged survival. Following GD2-targeted NIR-PIT, activation of host immunity was observed. In conclusion, GD2-targeted NIR-PIT was similarly effective to the conventional protein-targeted NIR-PIT. This study demonstrates that membrane glycolipid can be a new target of NIR-PIT.
Keyphrases
- cancer therapy
- photodynamic therapy
- drug release
- fluorescence imaging
- fluorescent probe
- drug delivery
- poor prognosis
- autism spectrum disorder
- stem cells
- magnetic resonance
- heart failure
- physical activity
- cell proliferation
- radiation therapy
- induced apoptosis
- magnetic resonance imaging
- left ventricular
- protein protein
- long non coding rna
- mental health
- endoplasmic reticulum stress
- climate change
- risk assessment
- atrial fibrillation
- single molecule
- light emitting