Search Results (50)

Immune checkpoint inhibitors (ICIs) have improved clinical outcomes in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), including oral squamous cell carcinoma (OSCC). However, many patients eventually develop resistance to systemic therapy, highlighting the need for novel strategies that can restore or sustain antitumor immunity. Near-infrared photoimmunotherapy (PIT) has emerged as a tumor-selective locoregional treatment that not only induces targeted tumor cell death but also promotes antitumor immune activation through immunogenic cell death. This narrative review summarizes current evidence regarding PIT for recurrent oral cancer and explores the immunological rationale for sequential ICI–PIT–ICI therapy (ICI–PIT–ICI sequence). Within this framework, PIT-induced tumor antigen release and inflammatory activation may reinitiate elements of the cancer-immunity cycle, whereas continued PD-1 blockade may help sustain newly activated tumor-reactive T-cell responses. To illustrate this concept, we present two cases of recurrent oral cancer treated with the ICI–PIT–ICI sequence. Both patients achieved durable clinical and radiological complete responses following PIT and subsequent nivolumab continuation. Longitudinal analyses of peripheral immune surrogate markers demonstrated a biphasic temporal pattern characterized by transient increases in inflammatory markers, including neutrophil-to-lymphocyte ratio, C-reactive protein, platelet-to-lymphocyte ratio, and systemic immune-inflammation index, followed by recovery trends in absolute lymphocyte count and lymphocyte-to-monocyte ratio during continued PD-1 blockade. These observations support the biological plausibility of PIT as an immune-modulating intervention with potential immune-reprogramming effects. Although hypothesis-generating, the ICI–PIT–ICI sequence may represent a promising strategy integrating locoregional tumor destruction with systemic immune modulation in recurrent oral cancer. Further prospective studies incorporating peripheral and tissue-based immune profiling are warranted. Full article

Background/Objectives: Near-infrared photoimmunotherapy (NIR-PIT) provides tumor-selective cytotoxicity with minimal collateral tissue damage and has emerged as a novel treatment option for recurrent head and neck squamous cell carcinoma (HNSCC). However, biomarkers that predict treatment response to NIR-PIT remain poorly defined. Therefore, this study aimed to exploratorily determine whether baseline nutritional and inflammatory composite biomarkers are associated with complete response to NIR-PIT in patients with recurrent HNSCC. Methods: Fifteen non-surgical candidates with recurrent HNSCC underwent NIR-PIT between January 2022 and December 2025. Baseline composite nutritional indices and inflammatory markers, including the systemic inflammation response index (SIRI), were assessed before and 4–8 weeks post-treatment. Tumor response was evaluated according to RECIST version 1.1. Exploratory comparisons between complete response (CR) and non-CR groups were performed using Wilcoxon rank-sum tests with effect size estimation. Results: Five of 15 patients achieved CR (33.3%). Baseline SIRI was significantly lower in the CR group than in the non-CR group (median 70.7 vs. 120.2; p = 0.03), with a large effect size (r = 0.55). In contrast, baseline composite nutritional indices and other inflammatory markers showed no significant association with treatment response. Nutritional status remained stable after NIR-PIT, as reflected by preserved nutritional index values. SIRI tended to increase post-treatment in patients who achieved CR. Conclusions: NIR-PIT achieved encouraging local tumor responses in recurrent HNSCC while preserving early nutritional status. Baseline SIRI may represent a potential inflammation-based correlate of CR, reflecting the balance between systemic inflammation and host immune status, and warrants validation in larger prospective cohorts. Full article

Background/Objectives: Near-infrared photoimmunotherapy (NIR-PIT) represents a treatment approach for patients with locally advanced or recurrent head and neck cancers who are unsuitable for surgery post-standard therapy. Since its introduction in Japan in January 2021, NIR-PIT has been available exclusively under the national health insurance system, resulting in limited real-world clinical practice data. This study evaluated the association between NIR-PIT and overall survival (OS) in clinical practice. Methods: This single-center retrospective study included 45 patients with head and neck cancer who were not amenable to surgical resection owing to advanced local disease or regional recurrence without distant metastasis and who underwent NIR-PIT or systemic pharmacotherapy between January 2021 and April 2025. The primary endpoint was OS. Results: Twenty-two and 23 patients received NIR-PIT and pharmacotherapy, respectively. In the NIR-PIT group, irradiation was delivered to primary tumors in 20 patients, cervical lymph node lesions in one, and both primary and lymph node lesions in one. The median OS was 35 and 8 months, with median follow-up of 40 and 49 months in the NIR-PIT and pharmacotherapy groups, respectively. Among the NIR-PIT-eligible patients, 22 and 10 were treated with NIR-PIT and pharmacotherapy, respectively. The median OS was 35 and 8 months, with median follow-up of 40 and 24 months in the NIR-PIT and pharmacotherapy groups, respectively. Conclusions: NIR-PIT was independently associated with improved OS in patients with unresectable recurrent or metastatic head and neck cancer without distant metastasis. Prospective multicenter studies are warranted to validate these findings. Full article

Near-infrared photoimmunotherapy (NIR-PIT) has recently attracted attention as a highly selective cancer treatment, with good treatment outcomes observed from the only antibody-based drug currently available for clinical use. However, since only a single agent is currently used clinically and the development of new antibodies is costly, exploring other therapeutic modalities is important. In this study, we investigated a novel peptide-based PIT drug targeting programmed death-ligand 1 (PD-L1), which is overexpressed in many types of cancer. The WL12 peptide, which is known to bind to PD-L1, was conjugated with the photoabsorber IRDye700DX (IR700), and its usefulness was evaluated in vitro and in vivo. In therapeutic experiments on PD-L1-positive cells, NIR-PIT with WL12-IR700 induced PIT-like morphological changes in cells and reduced cancer cell viability in an NIR light dose- and drug concentration-dependent manner. In vivo experiments showed significant suppression of tumor growth and an extended overall survival rate. These results indicate that the developed peptide-based drug can be used for PD-L1-targeted NIR-PIT. Full article

Background/Objectives: Near-infrared photoimmunotherapy (NIR-PIT) is a molecularly targeted cancer therapy that employs antibody–photoabsorber conjugates (APCs) comprising the photosensitizer IRDye700DX (IR700) and tumor-specific antibodies. Following near-infrared (NIR) light irradiation, IR700 undergoes structural modification, inducing selective and rapid necrotic cell death. In mouse tumor models, we observed that IR700 fluorescence decreased during irradiation but recovered immediately afterward. This study aimed to characterize this novel phenomenon, named “early fluorescence recovery,” and explore its therapeutic implications. Methods: Cetuximab-IR700 (Cet-IR700) was synthesized and administered to A431 and FaDu-Luc2 xenograft female BALB/c-nu/nu mouse models. In vivo fluorescence imaging was conducted using LIGHTVISION during and after NIR irradiation (690 nm, 50 J/cm²). Reactive oxygen species involvement was examined via intraperitoneal administration of L-sodium ascorbate. Tumor blood flow changes were assessed via indocyanine green (ICG) imaging, and therapeutic efficacy was compared between single and divided irradiation protocols. Results: Tumor fluorescence markedly decreased during NIR-PIT but rapidly recovered within 10 min after irradiation. This recovery was significantly inhibited by L-sodium ascorbate (p < 0.01) and accompanied by increased ICG fluorescence (p < 0.01), suggesting enhanced tumor perfusion. Divided irradiation performed after fluorescence recovery tended to yield greater tumor suppression than did single irradiation, although the difference was not statistically significant. Conclusions: Early fluorescence recovery after NIR-PIT reflects transient reactivation of photoactive APCs through oxygen-dependent molecular and vascular mechanisms. Exploiting this brief recovery window with divided irradiation may improve therapeutic efficacy and guide optimization of NIR-PIT protocols. Full article

Background/Objectives: Boron-dipyrromethene (BODIPY) derivatives are a superior class of fluorophores prized for their exceptional photostability and tunable photophysical properties. While ideal for imaging, their translation to photodynamic therapy (PDT) has been hampered by excitation in the visible range, leading to poor tissue penetration. To overcome this, intense research has focused on developing near-infrared (NIR)-absorbing BODIPY photosensitizers (PS). This review aims to systematically summarize the hierarchical design strategies, from molecular engineering to advanced nanoplatform construction, that underpin the recent progress of NIR-BODIPY PS in therapeutic applications. Methods: We conducted a comprehensive literature review using PubMed, Scopus, and Web of Science databases. The search focused on keywords such as “BODIPY”, “aza-BODIPY”, “near-infrared”, “photodynamic therapy”, “photothermal therapy”, “nanocarriers”, “hypoxia”, “immuno-phototherapy”, and “antibacterial.” This review analyzes key studies describing molecular design, chemical modification strategies (e.g., heavy-atom effect, π-extension), nanoplatform formulation, and therapeutic applications in vitro and in vivo. Results: Our analysis reveals a clear progression in design complexity. At the molecular level, we summarize strategies to enhance selectivity, including active targeting, designing “smart” PS responsive to the tumor microenvironment (TME) (e.g., hypoxia or low pH), and precise subcellular localization (e.g., mitochondria, lysosomes). We then detail the core chemical strategies for achieving NIR absorption and high singlet oxygen yield, including π-extension, the internal heavy-atom effect, and heavy-atom-free mechanisms (e.g., dimerization). The main body of the review categorizes the evolution of advanced theranostic nanoplatforms, including targeted systems, stimuli-responsive ‘smart’ systems, photo-immunotherapy (PIT) platforms inducing immunogenic cell death (ICD), hypoxia-overcoming systems, and synergistic chemo-phototherapy carriers. Finally, we highlight emerging applications beyond oncology, focusing on the use of NIR-BODIPY PS for antibacterial therapy and biofilm eradication. Conclusions: NIR-BODIPY photosensitizers are a highly versatile and powerful class of theranostic agents. The field is rapidly moving from simple molecules to sophisticated, multifunctional nanoplatforms designed to overcome key clinical hurdles like hypoxia, poor selectivity, and drug resistance. While challenges in scalability and clinical translation remain, the rational design strategies and expanding applications, including in infectious diseases, confirm that NIR-BODIPY derivatives will be foundational to the next generation of precision photomedicine. Full article

Background: Non-muscle invasive bladder cancer (NMIBC) has limited therapeutic options and high recurrence rates. Photoimmunotherapy (PIT) enables targeted tumor ablation using antibody-photosensitizer conjugates and light activation. We evaluated EGFR, Nectin-4, and TROP-2 as PIT targets using cysteine-modified antibodies conjugated to the photosensitizer WB692-CB2. Methods: Antibodies derived from Cetuximab (Cmb, anti-EGFR), Enfortumab (Enf, anti-Nectin-4), and Sacituzumab (Sac, anti-TROP-2) were engineered with T120C and D265C mutations in the heavy chains for site-specific dye conjugation. Binding of the conjugates to BC cells was tested by flow cytometry and light-induced cytotoxicity of the conjugates, alone or in combination, was assessed by viability assays following irradiation. Results: Cysteine-modified antibodies were produced as intact IgG molecules and were efficiently conjugated with WB692-CB2 without loss of antigen specificity. Sac^T120C/D265C-WB692-CB2 showed the highest target binding and achieved near-complete cell killing at a red-light dose of 32 J/cm². Cmb^T120C/D265C-WB692-CB2 required a fourfold higher light dose for comparable efficacy, while Enf^T120C/D265C-WB692-CB2 demonstrated lower potency. No cytotoxicity was observed in antigen-negative cells. Combined treatment enhanced cytotoxicity, indicating additive phototherapeutic effects. Conclusions: Our findings suggest that PIT targeting EGFR, Nectin-4, or TROP-2 merits further preclinical development as a targeted therapeutic approach for NMIBC, including potential combinatorial or personalized strategies. Full article

Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer treatment that utilizes antibody–photoabsorber (IRDye700DX [IR700]) conjugates and NIR light. Necrotic cell death associated with lethal membrane damage is induced when this conjugate binds to an antigen on cancer cells, and it is exposed to NIR light. Therefore, various membrane proteins are potential therapeutic targets for NIR-PIT, and many studies have described various target molecules and specific antibodies. To develop future drugs for NIR-PIT, the selection of appropriate target membrane proteins and monoclonal antibodies will be important. In this review, we summarize the membrane targets and antibodies for NIR-PIT used in previous studies, focusing on the characteristics of each molecule. Full article

Background/Objectives: Photoimmunotherapy for head and neck cancer (HN-PIT) is an emerging treatment for unresectable locally advanced or recurrent head and neck cancer. However, real-world data (RWD) are limited. This study examined the safety and effectiveness of HN-PIT. Methods: This multicenter, retrospective cohort study included 40 patients with unresectable locally advanced or recurrent head and neck cancers who underwent HN-PIT from January 2021 to August 2024. The primary endpoint was time to treatment failure (TTF). Secondary endpoints included the objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Results: The median TTF and 1-year treatment failure rate were 6.0 months and 23.2%, respectively. Moreover, the ORR, disease control rate, median OS, and median PFS were 75.0% (95% confidence interval [CI]: 60.0–86.0%), 95.0% (95% CI: 83.5–99.0%), 26.9 months, and 6.2 months, respectively. The incidence of grade ≥3 AEs was 17.5% (95% CI: 7.1–29.1%). Pain was the most common AE, occurring in 37 patients (92.5%), with grade III pain reported in 5 (12.5%). Mucositis occurred in 32 patients (80.0%), with grade III mucositis reported in 3 (7.5%). Hemorrhages occurred in 31 patients (77.5%), with no grade ≥III hemorrhages reported. Two patients experienced sepsis (5.0%; grades IV and V). Seventeen patients (42.5%) had laryngeal edema, with grade IV edema reported in four (10.0%). Conclusions: Our RWD shows that HN-PIT is effective with an acceptable safety profile. TTF may serve as an endpoint reflecting this treatment’s characteristics. This study provides important basic data for the development of future treatment strategies. Full article

Traditional oncological therapies have contributed to reducing the global cancer burden; however, they have not achieved complete eradication, nor have they effectively prevented relapses, minimized toxicity, or preserved immune function. Recent advances, particularly the introduction of immune checkpoint inhibitors (ICIs) and CAR-T cell therapies, have markedly improved clinical outcomes and overall survival in certain cancer subtypes. Nevertheless, response rates remain suboptimal, and adverse immunological events are frequent. This review starts by highlighting the FDA-approved ICIs currently utilized in cancer immunotherapy, emphasizing those that have demonstrated clinical efficacy in recent years. The true focus of our analysis is on the latest clinical applications of near-infrared photoimmunotherapy (NIR-PIT). This emerging modality is evaluated in patients with head and neck cancers (HNC), particularly in cases that are unresectable, locally advanced, or recurrent. Finally, the review explores the current landscape and prospects of NIR-PIT, considering its potential to enhance therapeutic efficacy and extend relapse-free survival. Photoimmunotherapy is a promising, molecularly targeted option for patients with limited prognosis, offering new hope where conventional therapies fail. By synthesizing recent clinical trial data, this work highlights how NIR-PIT could bridge the translational gap between preclinical research and clinical practice. The integration of advanced technologies and interdisciplinary collaboration among researchers, clinicians, and technologists will be critical in optimizing NIR-PIT, improving its accuracy, efficacy, and safety, and ultimately advancing standards of cancer care and patient survival. Full article

Near-infrared photoimmunotherapy (NIR-PIT) is a promising cancer treatment that uses near-infrared light to activate a conjugate of a monoclonal antibody (mAb) and a photoactivatable silica phthalocyanine dye (IRDye700DX: IR700). Unlike conventional photodynamic therapy (PDT), NIR-PIT selectively destroys targeted tumor cells while preserving the surrounding normal tissue and providing superior tissue penetration. Recently, NIR-PIT has been approved for the treatment of unresectable recurrent head and neck cancers in Japan. It induces highly selective cancer cell death; therefore, it is expected to be a new curative treatment option for various cancers, including brain tumors. In this review, we compare the principles of NIR-PIT and PDT and discuss the potential applications of NIR-PIT for brain tumors. We selected targetable proteins across various types of brain tumors and devised a strategy to effectively pass the mAb–IR700 conjugate through the blood–brain barrier (BBB), which is a significant challenge for NIR-PIT in treating brain tumors. Innovative approaches for delivering the mAb–IR700 conjugate across the BBB include exosomes, nanoparticle-based systems, and cell-penetrating peptides. Small-molecule compounds, such as affibodies, are anticipated to rapidly accumulate in tumors within intracranial models, and our preliminary experiments demonstrated rapid uptake. NIR-PIT also induces immunogenic cell death and activates the anti-tumor immune response. Overall, NIR-PIT is a promising approach for treating brain tumors. It has the potential to overcome the limitations of conventional therapies and offers new hope to patients with brain tumors. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC), which has a poor prognosis, involves an overabundance of fibroblasts and extracellular matrix. Cancer-associated fibroblasts (CAFs) are critical for providing structural support by secreting soluble factors and extracellular matrix proteins into the stroma. We assessed the potential of near-infrared photoimmunotherapy (NIR-PIT) targeting CAFs in PDAC. Methods: PDAC cells (Capan-1 and SUIT-2) and CAFs (hPSC-5) were used. Anti-human fibroblast activation protein (FAP)/podoplanin (PDPN) antibodies were used to bind to CAFs and conjugates with the specific photosensitizer IRDye^®700DX (IR700) to investigate the effects of NIR-PIT. Thereafter, BALB/c Slc-nu/nu mice were transplanted with Capan-1 and/or CAFs and treated with gemcitabine (GEM) with or without NIR-PIT. Results: The binding rate of anti-FAP antibody-AlexaFluor^®488 conjugate to hPSC-5 cells was high, whereas that of the anti-PDPN antibody-conjugate was not. The incubation of anti-FAP antibody-IR700 conjugate (αFAP-IR700) with hPSC-5 cells for 3 h led to maximal fluorescence on the surface of hPSC-5 cells. When NIR-PIT with αFAP-IR700 was performed in the co-culture group of Capan-1 and hPSC-5 cells, the proliferative capacity of Capan-1 cells decreased to the same level as that when Capan-1 cells were cultured alone (p < 0.05). In vivo, compared with the GEM group, the NIR-PIT with the GEM group showed a significant reduction in the tumor volume (day 28: 79 vs. 382 mm³, p < 0.05). Tumor volumes in the NIR-PIT group were not reduced compared with those in the control group. Conclusions: Combining NIR-PIT with conventional chemotherapy to target CAFs may enhance the anticancer effects on PDAC. Full article

Background: Seasonal influenza causes significant morbidity and mortality each year. Since viruses can easily acquire drug-resistant mutations, it is necessary to develop new antiviral strategies with different targets. Near-infrared photoimmunotherapy (NIR-PIT) is a type of anti-cancer therapy that has recently attracted considerable attention, with favorable outcomes reported for several cancers. In this study, we investigated whether this approach could be used as a novel anti-influenza therapy to destroy influenza virus and infected cells. Methods: To evaluate the efficacy of near-infrared antiviral photoimmunotherapy (NIR-AVPIT), we prepared an anti-hemagglutinin (HA) monoclonal antibody without neutralizing activity against influenza A virus (FluV) labeled with IR-700 and reacted it with FluV and infected cells, as well as HA-expressing HEK293 cells. Results: NIR-AVPIT strongly inactivated FluV virions, suppressed cytopathic effects, and achieved more than a 4-log reduction in viral RNA amplification. Treatment of FluV-infected cells with the antibody-IR700 complex and NIR in the early stages of infection significantly inhibited viral propagation, and double treatment with time apart exerted a greater inhibitory effect. NIR-AVPIT rapidly induced morphological changes in HA-expressing HEK293 cells and inhibited the proliferation of these cells. Conclusions: These results suggest that NIR-AVPIT targeting HA antigens could inactivate FluV and eliminate infected cells in vitro. This strategy is a promising approach to treat various viral infections, including influenza. Full article

Background/Objectives: Photoimmunotherapy (PIT) is an innovative approach for the targeted therapy of cancer. In PIT, photosensitizer dyes are conjugated to tumor-specific antibodies for targeted delivery into cancer cells. Upon irradiation with visible light, the photosensitizer dye is activated and induces cancer-specific cell death. In the present article, we describe the PIT of prostate cancer (PC) as a therapeutic option for the targeted treatment of localized prostate cancer. Methods: We conjugated the silicon phthalocyanine dye WB692-CB2 to recombinant cysteine-modified anti-CD44 and anti-EpCAM antibodies via a maleimide linker and tested the antibody dye conjugates for PIT on PC cells and prostate cancer stem cell (PCSC)-like cells. Results: The anti-CD44 and anti-EpCAM antibody dye conjugates showed specific binding and high cytotoxicity against PC and PCSC-like cells following irradiation with red light. Combined treatment with both conjugates led to enhanced cytotoxic effects. Conclusions: PIT with our dye WB692-CB2 can serve as an effective focal therapy against prostate cancer, preserving the prostate gland and minimizing side effects. It can be employed during radical prostatectomy (RP) to treat residual tumor cells or lymph node metastases in areas where further surgical intervention is not feasible. Utilizing multiple conjugates against antigens expressed on differentiated PC and PCSC-like cells, such as CD44 and EpCAM, could be an effective method to eradicate residual cancer cells in heterogeneous tumors. This approach could reduce the risk of local recurrence after RP and thus increase the therapeutic outcome of PC patients. Full article

Background/Objectives: Near-infrared photoimmunotherapy (NIR-PIT) was recently approved for the treatment of unresectable locally advanced or recurrent head and neck cancers in Japan; however, only one clinical dose has been validated in clinical trials, potentially resulting in excessive or insufficient dosing. Moreover, IRDye700X (IR700) fluorescence intensity plateaus during treatment, indicating a particular threshold for the antitumor effects. Therefore, we investigated the NIR laser dose across varying tumor sizes and irradiation methods until the antitumor effects of the fluorescence decay rate plateaued. Methods: Mice were subcutaneously transplanted with A431 xenografts and categorized into control, clinical dose (cylindrical irradiation at 100 J/cm², frontal irradiation at 50 J/cm²), and evaluation groups. The rate of tumor IR700 fluorescence intensity decay to reach predefined rates (−0.05%/s or −0.2%/s) until the cessation of light irradiation was calculated using a real-time fluorescence imaging system. Results: The evaluation group exhibited antitumor effects comparable to those of the clinical dose group at a low irradiation dose. Similar results were observed across tumor sizes and irradiation methods. Conclusions: In conclusion, the optimal antitumor effect of NIR-PIT is achieved when the fluorescence decay rate reaches a plateau, indicating the potential to determine the appropriate dose for PIT using a real-time fluorescence monitoring system. Full article