Near-infrared photoimmunotherapy: basics and clinical application

Abstract Use of antibody–drug conjugates (ADCs) is rapidly increasing in the field of oncology. While ADCs exhibit strong and cell-selective cytotoxicity, they do not show spatial selectivity. Near-infrared photoimmunotherapy (NIR-PIT, Alluminox™) utilizes photoactivatable ADCs, that is, antibody–photoabsorber conjugates (APCs). The photoabsorber used in NIR-PIT, IRDye700DX (IR700), is activated by light of ~690 nm wavelength. APCs, usually administered by intravenous injection, bind to the target cell surface, and subsequent excitation–light illumination dramatically changes the status of IR700 from hydrophilic to hydrophobic, inducing aggregation of the APC–target molecule complex and cell burst. Dying cells release neoantigens as well as damage-associated molecular patterns, resulting in immunogenic cell death (ICD). Based on the favorable results of clinical trials, epidermal growth factor–targeted NIR-PIT has been performed in Japan since 2021 for patients with unresectable head and neck cancers (HNCs). Since pain and local edema are frequent adverse events (AEs), various measures have been taken against these AEs. Because NIR-PIT induces ICD, combining NIR-PIT with immune checkpoint inhibitor (ICI) therapy is thought to be a rather effective strategy. NIR-PIT could also locally destroy immune suppressor cells, such as regulatory T cells, in the tumor microenvironment. Currently, numerous clinical trials are under way to evaluate the efficacy of NIR-PIT as well as of combined NIR-PIT plus ICI therapy. In this review article, we describe the basics of NIT-PIT, results of translational experiments, current clinical application of NIT-PIT in HNCs, and relevant ongoing clinical trials.