Near Infrared Photoimmunotherapy; A Review of Targets for Cancer Therapy

Abstract

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.

Keywords: cancer; cancer therapy; host immunity; near-infrared photoimmunotherapy (NIR-PIT); target molecule.

Figure 1

Scheme for cellular cytotoxicity induced by NIR-PIT. Antibody-photoabsorber conjugates bind to a specific cell membrane antigen. Immediately after NIR light exposure to APC, the water outside of the cells is flown into the target cell, leading to cell death. Adapted from Ref [10].

Figure 2

The positivity proportion of (A) EGFR and (B) HER2 expressions in various cancers (ca.; carcinoma, ESCC; esophageal squamous cell carcinoma, EAC; esophageal adenocarcinoma). ((A) The numbers in the brackets show reference number. (B) Quoted from references [50,51]).

Figure 3

Target molecule of NIR-PIT developed for cancer therapy. NIR-PIT can target not only various surface molecules expressing cancer cells but also immunosuppressive cells that compose the tumor microenvironment, such as regulatory T cells, tumor-associated macrophages, cancer-associated fibroblasts, and neovascularity.