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Near-infrared photoimmunotherapy: design and potential applications for cancer treatment and beyond.

ABSTRACT: Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment modality based on a target-specific photosensitizer conjugate (TSPC) composed of an NIR phthalocyanine photosensitizer and an antigen-specific recognition system. NIR-PIT has predominantly been used for targeted therapy of tumors via local irradiation with NIR light, following binding of TSPC to antigen-expressing cells. Physical stress-induced membrane damage is thought to be a major mechanism underlying NIR-PIT-triggered photokilling. Notably, NIR-PIT can rapidly induce immunogenic cell death and activate the adaptive immune response, thereby enabling its combination with immune checkpoint inhibitors. Furthermore, NIR-PIT-triggered "super-enhanced permeability and retention" effects can enhance drug delivery into tumors. Supported by its potential efficacy and safety, NIR-PIT is a rapidly developing therapeutic option for various cancers. Hence, this review seeks to provide an update on the (i) broad range of target molecules suitable for NIR-PIT, (ii) various types of receptor-selective ligands for designing the TSPC "magic bullet," (iii) NIR light parameters, and (iv) strategies for enhancing the efficacy of NIR-PIT. Moreover, we review the potential application of NIR-PIT, including the specific design and efficacy in 19 different cancer types, and its clinical studies. Finally, we summarize possible NIR-PIT applications in noncancerous conditions, including infection, pain, itching, metabolic disease, autoimmune disease, and tissue engineering.

SUBMITTER: Wei D

PROVIDER: S-EPMC9576624 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Near-infrared photoimmunotherapy: design and potential applications for cancer treatment and beyond.

Wei Danfeng D Qi Jinxin J Hamblin Michael R MR Wen Xiang X Jiang Xian X Yang Hao H

Theranostics 20221009 16

Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment modality based on a target-specific photosensitizer conjugate (TSPC) composed of an NIR phthalocyanine photosensitizer and an antigen-specific recognition system. NIR-PIT has predominantly been used for targeted therapy of tumors via local irradiation with NIR light, following binding of TSPC to antigen-expressing cells. Physical stress-induced membrane damage is thought to be a major mechanism underlying NIR-PIT-tr ...[more]

PMID: 36276636

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Project description:This Account is the first comprehensive review article on the newly developed, photochemistry-based cancer therapy near-infrared (NIR) photoimmunotherapy (PIT). NIR-PIT is a molecularly targeted phototherapy for cancer that is based on injecting a conjugate of a near-infrared, water-soluble, silicon-phthalocyanine derivative, IRdye700DX (IR700), and a monoclonal antibody (mAb) that targets an expressed antigen on the cancer cell surface. Subsequent local exposure to NIR light turns on this photochemical "death" switch, resulting in the rapid and highly selective immunogenic cell death (ICD) of targeted cancer cells. ICD occurs as early as 1 min after exposure to NIR light and results in irreversible morphologic changes only in target-expressing cells based on the newly discovered photoinduced ligand release reaction that induces physical changes on conjugated antibody/antigen complex resulting in functional damage on cell membrane. Meanwhile, immediately adjacent receptor-negative cells are totally unharmed. Because of its highly targeted nature, NIR-PIT carries few side effects and healing is rapid. Evaluation of the tumor microenvironment reveals that ICD induced by NIR-PIT results in rapid maturation of immature dendritic cells adjacent to dying cancer cells initiating a host anticancer immune response, resulting in repriming of polyclonal CD8+T cells against various released cancer antigens, which amplifies the therapeutic effect of NIR-PIT. NIR-PIT can target and treat virtually any cell surface antigens including cancer stem cell markers, that is, CD44 and CD133. A first-in-human phase 1/2 clinical trial of NIR-PIT using cetuximab-IR700 (RM1929) targeting EGFR in inoperable recurrent head and neck cancer patients successfully concluded in 2017 and led to "fast tracking" by the FDA and a phase 3 trial ( https://clinicaltrials.gov/ct2/show/NCT03769506 ) that is currently underway in 3 countries in Asia, US/Canada, and 4 countries in EU. The next step for NIR-PIT is to further exploit the immune response. Preclinical research in animals with intact immune systems has shown that NIT-PIT targeting of immunosuppressor cells within the tumor, such as regulatory T-cells, can further enhance tumor-cell-selective systemic host-immunity leading to significant responses in distant metastatic tumors, which are not treated with light. By combining cancer-targeting NIR-PIT and immune-activating NIR-PIT or other cancer immunotherapies, NIR-PIT of a local tumor, could lead to responses in distant metastases and may also inhibit recurrences due to activation of systemic anticancer immunity and long-term immune memory without the systemic autoimmune adverse effects often associated with immune checkpoint inhibitors. Furthermore, NIR-PIT also enhances nanodrug delivery into tumors up to 24-fold superior to untreated tumors with conventional EPR effects by intensively damaging cancer cells behind tumor vessels. We conclude by describing future advances in this novel photochemical cancer therapy that are likely to further enhance the efficacy of NIR-PIT.

Project description:BackgroundNear-infrared photoimmunotherapy (NIR-PIT) is an emerging cancer treatment technology that combines the advantages of optical technology and immunotherapy to provide a highly effective, precise, and low side-effect treatment approach. The aim of this study is to visualize the scientific results and research trends of NIR-PIT based on bibliometric analysis methods.MethodsThe Web of Science Core Collection (WoSCC) database was searched in August 2024 for relevant publications in the field of NIR-PIT. Data were analyzed using mainly CiteSpace and R software for bibliometric and visual analysis of the country/region, authors, journals, references and keywords of the publications in the field.ResultsA total of 245 publications were retrieved, including articles (n = 173, 70.61%) and reviews (n = 72, 29.39%). The annual and cumulative number of publications increased every year. The highest number of publications was from the United States (149, 60.82%), followed by Japan (70, 28.57%) and China (33, 13.47%). The research institution with the highest number of publications was National Institutes of Health (NIH)-USA (114, 46.53%). Kobayashi H (109) was involved in the highest number of publications, Mitsunaga M (211) was the most frequently cited in total. CANCERS (17) was the most frequently published journal, and NAT MED (220) was the most frequently co-cited journal. The top 10 keywords include near-infrared photoimmunotherapy (166), photodynamic therapy (61), monoclonal antibody (58), in vivo (50), cancer (46), expression (31), breast cancer (27), enhanced permeability (24), antibody (23), growth factor receptor (16). Cluster analysis based on the co-occurrence of keywords resulted in 13 clusters, which identified the current research hotspots and future trends of NIR-PIT in cancer treatment.ConclusionThis study systematically investigated the research hotspots and development trends of NIR-PIT in cancer treatment through bibliometric and visual analysis. As an emerging strategy, the research on the application of NIR-PIT in cancer treatment has significantly increased in recent years, mainly focusing on the targeting, immune activation mechanism, and treatment efficacy in solid tumors has received extensive attention. Future studies may focus on improving the efficacy and safety of NIR-PIT in cancer treatment, as well as developing novel photosensitizers and combination therapeutic regimens, and exploring the efficacy of its application in a wide range of solid tumors, which will provide an important reference and guidance for the application of NIR-PIT in clinical translation.

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Near-infrared photoimmunotherapy: design and potential applications for cancer treatment and beyond.

Publications

Near-infrared photoimmunotherapy: design and potential applications for cancer treatment and beyond.

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