Photoimmunotherapy

BACKGROUND: Noninvasive in vivo cell tracking is valuable in understanding the mechanisms that enhance anti-cancer immunity. We have recently developed a new method called phototruncation-assisted cell tracking (PACT), that uses photoconvertible cell tracking technology to detect in vivo cell migration. This method has the advantages of not requiring genetic engineering of cells and employing tissue-penetrant near-infrared light. METHODS: We applied PACT to monitor the migration of immune cells between a tumour and its tumour-draining lymph node (TDLN) after near-infrared photoimmunotherapy (NIR-PIT)...

A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy. Here, a new type of spatiotemporal biomimetic "Gemini nanoimmunoregulators" was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death (ICD), tumor-associated macrophages (TAMs) phenotype reprogramming and programmed cell death ligand 1 (PD-L1) degradation. The "Gemini nanoimmunoregulators" PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine (mPDA) as nanovectors to deliver metformin (Met) and toll-like receptor 7/8 agonist resiquimod (R848) to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane (RM) inlaid with T7 or M2 peptides...

The drug efficacy evaluation of tumor-selective photosensitive substances was expected to be enabled by imaging the fluorescence intensity in the tumor area. However, fluorescence observation is difficult during treatments that are performed during gastrointestinal endoscopy because of the challenges associated with including the fluorescence filter in the camera part. To address this issue, this study developed a device that integrates a narrow camera and a laser diffuser to enable fluorescence imaging through a forceps port...

INTRODUCTION: Implant infections caused by Staphylococcus aureus are responsible for high mortality and morbidity worldwide. Treatment of these infections can be difficult especially when bacterial biofilms are involved. In this study we investigate the potential of infrared photoimmunotherapy to eradicate staphylococcal infection in a mouse model. METHODS: A monoclonal antibody that targets Wall Teichoic Acid surface components of both S. aureus and its biofilm (4497-IgG1) was conjugated to a photosensitizer (IRDye700DX) and used as photoimmunotherapy in vitro and in vivo in mice with a subcutaneous implant pre-colonized with biofilm of Staphylococcus aureus...

Cancer progression and treatment-associated cellular stress impairs therapeutic outcome by inducing resistance. Endoplasmic reticulum (ER) stress is responsible for core events. Aberrant activation of stress sensors and their downstream components to disrupt homeostasis have emerged as vital regulators of tumor progression as well as response to cancer therapy. Here, an orchestrated nanophotoinducer (ERsNP) results in specific tumor ER-homing, induces hyperthermia and mounting oxidative stress associated reactive oxygen species (ROS), and provokes intense and lethal ER stress upon near-infrared laser irradiation...

Light-triggered phototherapies, such as photodynamic therapy (PDT) and photothermal therapy (PTT), have shown strong therapeutic efficacy with minimal invasiveness and systemic toxicity, offering opportunities for tumor-specific therapies. Phototherapies not only induce direct tumor cell killing, but also trigger anti-tumor immune responses by releasing various immune-stimulating factors. In recent years, conventional phototherapies have been combined with cancer immunotherapy as synergistic therapeutic modalities to eradicate cancer by exploiting the innate and adaptive immunity...

Cancer immunotherapy is expected to achieve tumor treatment mainly by stimulating the patient's own immune system to kill tumor cells. However, the low immunogenicity of the tumor and the poor efficiency of tumor antigen presentation result in a variety of solid tumors that do not respond to immunotherapy. Herein, we designed a proton-gradient-driven porphyrin-based liposome (PBL) with highly efficient Toll-like receptor 7 (TLR7) agonist (imiquimod, R837) encapsulation (R837@PBL). R837@PBL rapidly released R837 in the acid microenvironment to activate the TLR in the endosome inner membrane to promote bone-marrow-derived dendritic cell maturation and enhance antigen presentation...

Significant progress has been made in cancer immunotherapy; however, challenges such as interpatient variability, limited treatment response, and severe side effects persist. Although nanoimmunotherapy has emerged as a promising approach, the construction of precise and efficient nanosystems remain formidable challenges. Herein, a multifunctional nanoplatform was developed using macrophage-derived cellular vesicles (MCVs) for NIR-II imaging-guided precise cancer photo-immunotherapy. MCVs exhibited excellent tumor targeting and TAMs re-education effects, serving as both delivery carriers and therapeutic agents...

BACKGROUND: Within the last decade, poly(ADP-ribose) polymerase inhibitors (PARPi) have emerged in the clinic as an effective treatment for numerous malignancies. Preclinical data have demonstrated powerful combination effects of PARPi paired with photodynamic therapy (PDT), which involves light-activation of specialized dyes (photosensitizers) to stimulate cancer cell death through reactive oxygen species generation. RESULTS: In this report, the most potent clinical PARP inhibitor, talazoparib, is loaded into the core of a polymeric nanoparticle (NP-Tal), which is interfaced with antibody-photosensitizer conjugates (photoimmunoconjugates, PICs) to form PIC-NP-Tal...

INTRODUCTION: Head and neck photoimmunotherapy (HN-PIT) uses a combination of drugs and laser illumination to specifically destroy tumor cells. Lemierre's syndrome is an infectious disease with severe systemic symptoms caused by prior infection in the pharyngeal region, leading to thrombophlebitis. Here, we report a case of Lemierre's syndrome that developed after HN-PIT for recurrent nasopharyngeal carcinoma. CASE PRESENTATION: A 68-year-old male with nasopharyngeal carcinoma (squamous cell carcinoma) underwent HN-PIT after local recurrence with chemoradiation therapy...

Near-infrared photoimmunotherapy(NIR-PIT)is a novel cancer treatment modality that employs antibody-IRDye700DX (IR700)conjugates. Recently, the clinical application of NIR-PIT has received approval in Japan for patients with inoperable head and neck cancer, specifically targeting the human epidermal growth factor receptor(hEGFR). Furthermore, NIR-PIT extends beyond the scope of tumor antigens and can be employed to eliminate specific host cells that contribute to the creation of immune-permissive environments supporting tumor growth...

INTRODUCTION: Head and neck photoimmunotherapy (HN-PIT) has been conditionally approved by the Japanese government for the treatment of unresectable locally advanced or locally recurrent head and neck cancer since January 2021. HN-PIT makes local treatment of locally recurrent disease possible in cases where systemic drug therapy would have previously been the only option. However, when treatment is ineffective and the disease progresses, it is necessary to shift to conventional drug therapies...

Nanomedicine in combination with immunotherapy has shown great potential in the cancer treatment, but phototherapeutic nanomaterials that specifically activate the immunopharmacological effects in deep tumors have rarely been developed due to limited laser penetration depth and tumor immune microenvironment. Herein we report a newly synthesized semiconducting polymer grafted with imiquimod R837 and indoxmid encapsulated micelle (SPRIN-micelle) with strong absorption in the second near infrared window (NIR-II) that can relieve tumor immunosuppression and enhance the photothermal immunotherapy and catabolic modulation on tumors...

Cancer-associated fibroblasts (CAFs) constitute a prominent cellular component of the tumor stroma, with various pro-tumorigenic roles. Numerous attempts to target fibroblast activation protein (FAP), a highly expressed marker in immunosuppressive CAFs, have failed to demonstrate anti-tumor efficacy in human clinical trials. Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor therapy that utilizes an antibody-photo-absorbing conjugate activated by near-infrared light. In this study, we examined the therapeutic efficacy of CAF depletion by NIR-PIT in two mouse tumor models...

Enfortumab vedotin (EV), an antibody-drug conjugate (ADC) that targets Nectin-4, has shown promising results in the treatment of bladder cancer. However, multiple resistance mechanisms that are unique to ADCs limit the therapeutic potential of EV in clinical practice. Here, we developed and tested a Nectin-4-targeted near-infrared photoimmunotherapy (NIR-PIT) that utilizes the same target as EV but utilizes a distinct cytotoxic and immunotherapeutic pathway in preclinical models of bladder cancer. NIR-PIT was effective in vitro against luminal subtype human bladder cancer cell lines (RT4, RT112, MGH-U3, SW780, and HT1376-luc), but not against other subtype cell lines (UMUC3 and T24)...

Antibody-drug conjugates (ADCs) represent a therapeutic class of agents designed to selectively deliver cytotoxic payloads to cancer cells. With the increasingly positioning of ADCs in the clinical practice, combinations with other treatment modalities, including radiation therapy (RT), will open new opportunities but also challenges. This review evaluates ADC-RT interactions, examining therapeutic synergies and potential caveats. ADC payloads can be radiosensitizing, enhancing cytotoxicity when used in combination with RT...

Pancreatic ductal adenocarcinoma (PDAC) is notorious for its resistance against chemotherapy and immunotherapy due to its dense desmoplastic and immunosuppressive tumor microenvironment (TME). Traditional photodynamic therapy (PDT) was also less effective for PDAC owing to poor selectivity, insufficient penetration, and accumulation of photosensitizers in tumor sites. Here, we designed a light-responsive novel nanoplatform targeting the TME of PDAC through tumor-specific midkine nanobodies (Nbs), which could efficiently deliver semiconducting polymeric nanoparticles (NPs) to the TME of PDAC and locally produce abundant reactive oxygen species (ROS) for precise photoimmunotherapy...

Immunogenic cell death (ICD) is associated with the release of damage-associated molecular patterns, including ATP, to promote an effective immune cycle against tumors. However, tumors have evolved an effective strategy for degrading extracellular immunostimulatory ATP via the ATP-adenosine axis, allowing the sequential action of the ectonucleotidases CD39 to degrade accumulated immunostimulatory ATP into pleiotropic immunosuppressive adenosine. Here, an ingenious dissolving microneedle patch (DMNs) is designed for the intralesional delivery of CD39 inhibitor (sodium polyoxotungstate, POM-1) and ICD inducer (IR780) co-encapsulated solid lipid nanoparticles (P/I SLNs) for antitumor therapy...

DNA-templated metallization has emerged as an efficient strategy for creating nanoscale-metal DNA hybrid structures with a desirable conformation and function. Despite the potential of DNA-metal hybrids, their use as combinatory therapeutic agents has rarely been examined. Herein, we present a simple approach for fabricating a multipurpose DNA superstructure that serves as an efficient photoimmunotherapy agent. Specifically, we adsorb and locally concentrate Au ions onto DNA superstructures through induced local reduction, resulting in the formation of Au nanoclusters...

BACKGROUND/AIM: Head and neck photoimmuno-therapy (HN-PIT) has been an insured treatment in Japan for approximately three years. The number of treatments has gradually increased to over 350 cases. However, there are still various questions in actual clinical practice, including laryngeal edema. Therefore, it is vital to carefully explain in advance to patients the possibility of laryngeal edema occurring and obtaining consent for tracheostomy as a prophylactic or emergency measure. At our institution, 44 HN-PIT cycles were performed in 23 patients between January 2021 and October 2023...