Near-infrared photoimmunotherapy of cancer: a new approach that kills cancer cells and enhances anti-cancer host immunity

• Published in: International immunology Vol. 33; no. 1; pp. 7 - 15
• Main Authors: Kobayashi, Hisataka, Furusawa, Aki, Rosenberg, Adrian, Choyke, Peter L
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 01-01-2021
• Subjects: Antigens, Neoplasm - immunology; Antineoplastic Agents, Immunological - therapeutic use; Cell Line, Tumor; Cetuximab - therapeutic use; Combined Modality Therapy; Dendritic Cells - immunology; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - immunology; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - therapy; Humans; Immunotherapy - methods; Indoles - therapeutic use; Infrared Rays - therapeutic use; Invited Reviews; Lymphocyte Activation - immunology; Organosilicon Compounds - therapeutic use; T-Lymphocytes, Cytotoxic - immunology; imaging biomarker; multi-clonal immune response; immunogenic cell death; immunotherapy; regulatory cells
• ISSN: 1460-2377; 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxaa037

Abstract
Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed hybrid cancer therapy that directly kills cancer cells as well as producing a therapeutic host immune response. Conventional immunotherapies, such as immune-activating cytokine therapy, checkpoint inhibition, engineered T cells and suppressor cell depletion, do not directly destroy cancer cells, but rely exclusively on activating the immune system. NIR-PIT selectively destroys cancer cells, leading to immunogenic cell death that initiates local immune reactions to released cancer antigens from dying cancer cells. These are characterized by rapid maturation of dendritic cells and priming of multi-clonal cancer-specific cytotoxic T cells that kill cells that escaped the initial direct effects of NIR-PIT. The NIR-PIT can be applied to a wide variety of cancers either as monotherapy or in combination with conventional immune therapies to further activate anti-cancer immunity. A global Phase 3 clinical trial (https://clinicaltrials.gov/ct2/show/NCT03769506) of NIR-PIT targeting the epidermal growth factor receptor (EGFR) in patients with recurrent head and neck cancer is underway, employing RM1929/ASP1929, a conjugate of anti-EGFR antibody (cetuximab) plus the photo-absorber IRDye700DX (IR700). NIR-PIT has been given fast-track recognition by regulators in the USA and Japan. A variety of imaging methods, including direct IR700 fluorescence imaging, can be used to monitor NIR-PIT. As experience with NIR-PIT grows, additional antibodies will be employed to target additional antigens on other cancers or to target immune-suppressor cells to enhance host immunity. NIR-PIT will be particularly important in patients with localized and locally advanced cancers and may help such patients avoid side-effects associated with surgery, radiation and chemotherapy.
Near-infared photoimmunotherapy of cancer