Near Infrared Photoimmunotherapy; A Review of Targets for Cancer Therapy

Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that uses an antibody-photoabsorber (IRDye700DX) conjugate (APC) that is activated by NIR light irradiation. In September 2020, the first APC and laser system were conditionally approved for clinical use in Japan. A major benefit of NIR-PIT is that only APC-bound cancer cells that are exposed to NIR light are killed by NIR-PIT; thus, minimal damage occurs in adjacent normal cells. These early trials have demonstrated that in addition to direct cell killing, there is a significant therapeutic host immune response that greatly contributes to the success of the therapy. Although the first clinical use of NIR-PIT targeted epidermal growth factor receptor (EGFR), many other targets are suitable for NIR-PIT. NIR-PIT has now been applied to many cancers expressing various cell-surface target proteins using monoclonal antibodies designed to bind to them. Moreover, NIR-PIT is not limited to tumor antigens but can also be used to kill specific host cells that create immune-permissive environments in which tumors grow. Moreover, multiple targets can be treated simultaneously with NIR-PIT using a cocktail of APCs. NIR-PIT can be used in combination with other therapies, such as immune checkpoint inhibitors, to enhance the therapeutic effect. Thus, NIR-PIT has great potential to treat a wide variety of cancers by targeting appropriate tumor cells, immune cells, or both, and can be augmented by other immunotherapies

Usefulness of three-dimensional image navigation system for evaluation of hepatic artery before living donor liver transplantation: a case report

Abstract Background The evaluation of the hepatic vascular anatomy in living liver donors is increasingly being performed by three-dimensional (3D) computed tomography (CT) angiography. However, details of hepatic artery anatomy obtained by 3D CT angiography are not always superior to those obtained by angiography. Here, we report a case in which the 3D image navigation system helped to detect segment II, III, and IV arteries (A2, A3, and A4, respectively) that individually originated from the proper hepatic artery (PHA); this could not be detected by 3D CT angiography. Case presentation A 46-year-old man with end-stage primary biliary cirrhosis was admitted to our hospital for evaluation as a candidate for living donor liver transplantation. The patient’s younger sister, aged 43 years, was the only living donor candidate. The predicted left liver graft volume with the middle hepatic vein was found to be 403 mL using the region-growing method with 3D CT software. This volume was sufficiently large for the recipient because the standard liver volume of the recipient was 1095 mL. 3D CT angiography was performed twice but could not reveal the anatomical structure of the left and middle hepatic arteries. However, simulation using the region-growing method demonstrated individual branching off of A2, A3, and A4 from the PHA; conventional angiography demonstrated the same results. Each branch was approximately 1 mm in diameter, which was too small for secure anastomosis. Therefore, we selected the right liver graft for simplicity. The postoperative course of the donor and recipient was uneventful, and they were discharged on postoperative days 10 and 46, respectively. Conclusions In conclusion, reconstruction of the hepatic vasculature using the 3D software by region-growing method might be a useful adjunct for surgical planning in the evaluation of the hepatic arteries in living liver donors

Wound healing after excision of subcutaneous tumors treated with near‐infrared photoimmunotherapy

Abstract Near‐infrared photoimmunotherapy (NIR‐PIT) is a novel cancer therapy that employs a combination of infrared light and tumor‐targeted monoclonal antibody‐photoabsorber conjugates to cause both direct tumor necrosis and immunogenic cell death. NIR‐PIT may have potential in the perioperative setting before surgery, and therefore it is important to know the effect of NIR‐PIT on wound healing. Fifty mice were implanted with subcutaneous xenografts of N87 human gastric cancer cells, and tumors were excised after reaching a predetermined size. After excision, 30 mice were split into three groups: Controls, NIR‐PIT 1 day prior to surgery and NIR‐PIT 3 days prior to surgery. The quantity of reactive oxygen species (ROS) in each wound was measured on Postoperative Days 2 and 4, and mice were monitored weekly for 4 weeks for evidence of local tumor recurrence as well as clinical evidence of wound healing complications (eg, dehiscence, infection). The remaining 20 mice (10 controls, 10 treated with NIR‐PIT 1 day prior to surgery) were sacrificed on either Postoperative Day 7 or 14, the skin around wounds were excised, and tensile strength was measured with a digital force gauge. There were no significant differences between treatment and control groups with respect to wound ROS levels, wound tensile strength, local tumor recurrence, or postoperative complication rates (P > .05). In conclusion, neoadjuvant (pre‐operative) NIR‐PIT shows no evidence of adverse wound healing effects, and it is likely a safe adjunctive treatment to surgery. Postoperative use of NIR‐PIT merits investigation

Additional radiotherapy following endoscopic submucosal dissection for T1a-MM/T1b-SM esophageal squamous cell carcinoma improves locoregional control

Abstract Background Endoscopic submucosal dissection (ESD) can be used as a less invasive treatment option for superficial esophageal cancer involving the muscularis mucosae (T1a-MM) or upper third of the submucosa (T1b-SM1). Additional treatment after ESD is needed to prevent lymph node metastasis. However, the efficacy of radiotherapy following ESD has not been well evaluated. Moreover, the clinical outcomes of patients with large mucosal defects of the esophagus who received radiotherapy after ESD have not been reported. This study aimed to clarify the efficacy of additional radiotherapy following ESD for esophageal squamous cell cancer involving T1a-MM or T1b-SM1. Methods We analyzed twenty-seven patients with pathologically confirmed T1a-MM or T1b-SM1 esophageal squamous cell cancer treated by ESD. Thirteen patients received additional radiotherapy (RT group), and the remaining patients did not (non-RT group). Locoregional control (LRC), overall survival, cause-specific survival, and adverse events including treatment-related esophageal strictures were evaluated. Results The three-year LRC was significantly better for the RT than the non-RT group (100% vs. 57.8%, respectively; p = 0.022). Chemotherapy following ESD did not improve LRC. Multivariate analysis showed that radiotherapy was an independent prognostic factor for better LRC (p = 0.0022). Contrary to the results in LRC, overall and cause-specific survival were not significantly different between the RT and non-RT groups. A subgroup analysis of patients with mucosal defects involving ≥ 3/4 of the esophageal circumference after ESD showed that LRC of the RT group was better than that of the non-RT group (p = 0.049). Treatment-related esophageal strictures were observed in 2 of 6 patients in the RT group with large mucosal defects after ESD. No patients with mucosal defects involving less than 3/4 of the circumference after ESD developed treatment-related strictures. Conclusions Radiotherapy after ESD contributed to better LRC in esophageal squamous cell cancer involving pT1a-MM and pT1b-SM1. Esophageal strictures were observed in some patients with large mucosal defects after ESD. Despite leading to better LRC, radiotherapy after ESD should be undertaken after careful consideration for patients with large mucosal defects after ESD

Disialoganglioside GD2-Targeted Near-Infrared Photoimmunotherapy (NIR-PIT) in Tumors of Neuroectodermal Origin

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