Near infrared photoimmunotherapy of cancer; possible clinical applications

Abstract

Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that uses an antibody-photo-absorber conjugate (APC) composed of a targeting monoclonal antibody conjugated with a photoactivatable phthalocyanine-derivative dye, IRDye700DX (IR700). APCs injected into the body can bind to cancer cells where they are activated by local exposure to NIR light typically delivered by a NIR laser. NIR light alters the APC chemical conformation inducing damage to cancer cell membranes, resulting in necrotic cell death within minutes of light exposure. NIR-PIT selectivity kills cancer cells by immunogenic cell death (ICD) with minimal damage to adjacent normal cells thus, leading to rapid recovery by the patient. Moreover, since NIR-PIT induces ICD only on cancer cells, NIR-PIT initiates and activates antitumor host immunity that could be further enhanced when combined with immune checkpoint inhibition. NIR-PIT induces dramatic changes in the tumor vascularity causing the super-enhanced permeability and retention (SUPR) effect that dramatically enhances nanodrug delivery to the tumor bed. Currently, a worldwide Phase 3 study of NIR-PIT for recurrent or inoperable head and neck cancer patients is underway. In September 2020, the first APC and accompanying laser system were conditionally approved for clinical use in Japan. In this review, we introduce NIR-PIT and the SUPR effect and summarize possible applications of NIR-PIT in a variety of cancers.

Keywords: anti-cancer host immunity; cancer; immunogenic cell death; near-infrared photoimmunotherapy (NIR-PIT); super-enhanced permeability and retention (SUPR) effects.

Figure 1:

The mechanisms of cell death caused by NIR-PIT. (A) Structural change of IR700. Upon NIR light exposure, axial ligands are released from the IR700 molecule. Adapted from Ref. [8]. (B) Scheme of the cell killing mechanism induced by NIR-PIT. An antibody–IR700–antigen complex is formed on the antigen on the cell membrane. The conformational change of conjugate produces physical stress in the cell membrane, resulting in the weakening and rupture of the cell membrane. The water outside of the cell is flown into the cell, leading cell death. Adapted from Ref. [8].

Figure 2:

The mechanisms of SUPR effects induced by NIR-PIT. (A) Scheme of SUPR effect induced by NIR-PIT. Many of the initial cell killing occurs in the perivascular layer of tumor cells after NIR-PIT, leading to form a potential space around the tumor vasculature. It increases vascular permeability and decreases interstitial pressures. Then, nanodrug delivery to the remaining tumor can be enhanced. Adapted from Ref. [8]. (B) The increases of PEGylated quantum dot 800 into tumor bed 1 h after NIR-PIT were observed compared to control tumors (up to 24-fold). Adapted from Ref. [8].

Figure 3:

Various cancers and promising targets for NIR-PIT.