Near infrared photoimmunotherapy for cancers: A translational perspective

Abstract

Near-infrared photoimmunotherapy (NIR-PIT) is a newly-developed, highly-selective cancer treatment, which utilizes a monoclonal antibody conjugated to a photoabsorbing dye, IRDye700DX (IR700). The antibody conjugate is injected into the patient and accumulates in the tumour. Within 24 h of injection the tumour is exposed to NIR light which activates the conjugate and causes rapid, selective cancer cell death. A global phase III clinical trial of NIR-PIT in recurrent head and neck squamous cell cancer (HNSCC) patients is currently underway. Conditional clinical approval for NIR-PIT in recurrent HNSCC has been granted in Japan as of September 2020. Not only does NIR-PIT induce highly selective and immediate cancer cell killing, but it also stimulates highly active anti-tumour immunity. While monotherapy with NIR-PIT has proven effective it is likely that combinations with immune-checkpoint inhibitors or additional NIR-PIT targeting immune suppressive cells in the tumour microenvironment will further improve results. In this review, we discuss the translational aspects of NIR-PIT especially in HNSCC, and potential future applications.

EGFR-Targeted Photodynamic Therapy

“…The complex mechanism of killing exerted by the panitumumab-IR700DX (pan-IR700) and cetuximab-IR700DX (cet-IR700) conjugates has been investigated in detail in recent years using a wide panel of in vitro and in vivo tumor models. It became immediately clear that the conjugation of a PS with mAb was not only a strategy able to improve the targeting capability of PDT, but also a means to potentiate anticancer antibody therapies (photoimmunotherapy-PIT) [171][172][173].…”

“…In vivo, different modalities of light delivery were tested, from the use of interstitial light diffusers to implanted wireless LEDs [159,[164][165][166]; (6) The PIT treatment causes a large increase (up to 24-fold compared with untreated tumors) in vascular permeability that facilitates the delivery of intravenous therapeutics, resulting in a synergy between PIT and chemotherapy. This phenomenon is referred to as super-enhanced permeability and retention (SUPR) [148,156,174]; (7) PIT treatment causes an "immunogenic cell death" (ICD) [160,[171][172][173]. Upon PIT treatment, cancer-specific antigens and membrane damage markers are produced.…”

“…PIT could, therefore, have an advantage over conventional immunotherapies, which are hampered by heterogeneous or poor delivery of antibodies or immunoconjugates, since the cancer cells escaping the first line of irradiation-mediated ROS production could be cleared by the activated (cytotoxic) T cells. Moreover, since PIT can be repeatedly applied, multiple NIR-PIT treatments could also reinforce the APC-mediated priming of the cellular immune responses against the tumor [171][172][173]; (8) The therapeutic effects of NIR-PIT therapy can be monitored with several different imaging modalities. Exploiting the fluorescent properties of the used photosensitizers, it is possible to detect whether the antibody-PS conjugate has bound to the cancer cells and to set the proper light dosimetry, measuring the photobleaching of the PS.…”

Supramolecular cancer photoimmunotherapy based on precise peptide self-assembly design

“…Based on these therapeutic advantages, photoimmunotherapy has obtained encouraging results both in preclinical and clinical research of a number of cancers. 6,7 Especially, the first EGFR targeted NIR-PIT drug (ASP-1929, Akalux™, Rakten Medical Inc.) and a diode laser system (BioBlade™, Rakten Medical Inc.) were conditionally approved and registered for clinical use by the Pharmaceuticals and Medical Devices Agency in Japan in September 2020, 8,9 which demonstrates that photoimmunotherapy is very promising in clinical cancer treatment.…”

Combination of Near-Infrared Photoimmunotherapy Using Trastuzumab and Small Protein Mimetic for HER2-Positive Breast Cancer

“…Near-infrared photoimmunotherapy (NIR-PIT) is a promising cancer therapy using a monoclonal antibody-conjugated photosensitizer (IR700Dye) and near-infrared light, causing necrotic cancer cell death without an effect on normal cells [7][8][9]. In NIR-PIT, monoclonal antibody (mAb)-conjugated IR700Dye binds to a specific protein on the target cell surface, and when near-infrared light (690 nm) is irradiated, the light excites the IR700Dye, causing damage to the cell membrane [10]. Currently, NIR-PIT targeting EGFR with an mAb-IR700Dye conjugate is under a global phase III clinical evaluation for the treatment of head and neck cancer (NCT03769506).…”