Near infrared photoimmunotherapy for cancers: A translational perspective.
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ABSTRACT:
SUBMITTER: Maruoka Y
PROVIDER: S-EPMC8340111 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Near-infrared photoimmunotherapy (NIR-PIT) is a novel molecularly-targeted therapy that selectively kills cancer cells by systemically injecting an antibody-photoabsorber conjugate (APC) that binds to cancer cells, followed by the application of NIR light that drives photochemical transformations of the APC. APCs are synthesized by selecting a monoclonal antibody that binds to a receptor on a cancer cell and conjugating it to IRDye700DX silica-phthalocyanine dye. Approximately 24 h after APC administration, NIR light is delivered to the tumor, resulting in nearly-immediate necrotic cell death of cancer cells while causing no harm to normal tissues. In addition, NIR-PIT induces a strong immunologic effect, activating anti-cancer immunity that can be further boosted when combined with either immune checkpoint inhibitors or immune suppressive cell-targeted (e.g., regulatory T cells) NIR-PIT. Currently, a global phase III study of NIR-PIT in recurrent head and neck squamous cell carcinoma is ongoing. The first APC and NIR laser systems were approved for clinical use in September 2020 in Japan. In the near future, the clinical applications of NIR-PIT will expand to other cancers, including urologic cancers. In this review, we provide an overview of NIR-PIT and its possible applications in urologic cancers.
| S-EPMC9221010 | biostudies-literature
Project description:BackgroundCancers of the gastrointestinal (GI) tract are the common leading cause of cancer-related death in the world. Recent advances in cancer therapies such as intensive multidrug chemotherapy and molecular targeted treatment have improved therapeutic efficacy; however, the outcomes are not satisfied. Moreover, these therapies also cause severe side effects. New type of cancer therapies is urgently needed to improve the outcomes and to reduce side effects of GI tract cancers.SummaryThis account is a comprehensive review article on the newly developed, photochemistry-based cancer therapy named as near-infrared photoimmunotherapy (NIR-PIT). NIR-PIT is a highly selective tumor treatment that employs an antibody-photoabsorber conjugate, which is activated by near-infrared light. A world-wide phase 3 clinical trial of NIR-PIT against recurrent head and neck cancer patients is currently underway. NIR-PIT differs from conventional cancer therapies such as surgery, chemotherapy, and radiation in its selectivity for killing cancer cells and cells treated with NIR-PIT leading to immunogenic cell death. Preclinical research in animals with combining cancer-targeting NIR-PIT and other cancer immunotherapies could lead to responses not only in local tumor but also in distant metastases. NIR-PIT also leads to an immediate and dramatic increase in vascular permeability after therapy. From these aspects, NIR-PIT appears to be a promising new form of cancer therapy. NIR-PIT could be readily translated into clinical use for virtually any cancers in the near future provided suitable humanized antibodies are available. Here, we describe the specific advantages and applications of NIR-PIT in the GI tract. Key Messages: We believe that NIR-PIT with NIR excitation light, which can be delivered via a fiber optic diffuser through endoscopes, is a promising method for a new treatment of GI cancers.
| S-EPMC8200364 | biostudies-literature
Project description:Near-infrared photoimmunotherapy (NIR-PIT) is a molecularly targeted cancer phototherapy that is based on injecting a conjugate of a silicon-phthalocyanine derivative, IRdye 700DX (IR700), and a monoclonal antibody that targets an expressed antigen on the cancer cell surface. Subsequent local exposure to NIR light results in the rapid and highly selective immunogenic cell death of targeted cancer cells. Because many cancers grow in bones through which light does not penetrate well, the goal of this study was to determine if NIR-PIT can effectively treat cancers in bone. A bovine rib was used as a bone sample. Because the sample's NIR light transmittance was shown to be approximately 4.52% in preliminary tests, it was hypothesized that a maximum radiation dosage of 128 and 1500 J/cm2 would be sufficient to induce cell death in in vitro target cells and in vivo mouse tumor models, respectively. Cell viability was measured through bioluminescence studies comparing relative luciferase activity, as well as a cytotoxicity assay. In the in vitro model, tumor cell viability was significantly decreased after 64 and 128 J/cm2 NIR light irradiation through the bone. An in vivo mouse tumor model also showed that 1500 J/cm2 NIR light irradiation through the bone significantly reduced tumor viability at both 24 and 48 hours posttreatment compared to the control group (P = .026 and .040 respectively). Therefore, despite limitations in light transmission, NIR-PIT nevertheless is capable of effectively treating cancers within bone.
| S-EPMC6890452 | biostudies-literature
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.
| S-EPMC6704485 | biostudies-literature
Project description:Lung metastases are a leading cause of cancer related deaths; nonetheless current treatments are limited. Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies that target tumors with the toxicity induced by photosensitizers activated by NIR-light. Herein, we demonstrate the efficacy of NIR-PIT in a mouse model of lung metastases. Experiments were conducted with a HER2, luciferase and GFP expressing cell line (3T3/HER2-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye700DX, was synthesized. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. With 3D culture, repeated NIR-PIT could eradicate entire spheroids. In vivo anti-tumor effects of NIR-PIT included significant reductions in both tumor volume (p?=?0.0141 vs. APC) and bioluminescence image (BLI) (p?=?0.0086 vs. APC) in the flank model, and prolonged survival (p?<?0.0001). BLI demonstrated a significant reduction in lung metastases volume (p?=?0.0117 vs. APC). Multiple NIR-PIT doses significantly prolonged survival in the lung metastasis model (p?<?0.0001). These results suggested that NIR-PIT is a potential new therapy for the local control of lung metastases.
| S-EPMC4508660 | biostudies-literature
Project description:Human papillomavirus (HPV)-associated oropharyngeal cancer has a better prognosis than other head and neck cancers. However, rates of recurrence and metastasis are similar and the prognosis of recurrent or metastatic HPV-associated oropharyngeal cancer is poor. Near-infrared photoimmunotherapy (NIR-PIT) is a treatment involving administration of a photosensitizer (IRDye®700DX) conjugated to a monoclonal antibody followed by activation with near-infrared light illumination. It is a highly tumor-specific therapy with minimal toxicity in normal tissues. Moreover, NIR-PIT is expected to have not only direct effects on a treated lesion but also immune responses on untreated distant lesions. NIR-PIT with cetuximab-IR700 (AlluminoxTM) has been in routine clinical use since January 2021 for unresectable locally advanced or locally recurrent head and neck cancer in patients that have previously undergone radiotherapy in Japan. NIR-PIT for head and neck cancer (HN-PIT) is expected to provide a curative treatment option for the locoregional recurrent or metastatic disease after radiotherapy and surgery. This article reviews the mechanism underlying the effect of NIR-PIT and recent clinical trials of NIR-PIT for head and neck cancers, treatment-specific adverse events, combination treatment with immune checkpoint inhibitors, illumination approach and posttreatment quality of life, and provides a case of series of two patients who receive NIR-PIT for oropharyngeal cancer at our institution.
| S-EPMC9688155 | biostudies-literature
Project description:Near infrared photoimmunotherapy (NIR-PIT) is a new, highly-selective cancer theranostics that employs an antibody-photo absorber conjugate (APC). NIR-PIT has successfully treated preclinical tumor models with APCs and is now in the first-in-human phase 1 clinical trial for head and neck cancer patients against EGFR. CD20 is highly expressed in many B-cell lymphomas and is emerging as a molecular target for this disease. Here, we describe the use of the anti-CD20 monoclonal antibody (mAb), rituximab-IR700 APC for NIR-PIT of B-cell lymphoma in two CD20-expressing lymphoma mouse models. CD20 expressing B-cell lymphoma cell lines (Daudi and Ramos) were used in this study. Rituximab-IR700, rituximab conjugated with IRDye700DX, showed specific binding, and cell-specific killing only after exposure of NIR light to both cells in vitro. To evaluate effects of NIR-PIT in vivo, tumor-bearing mice were separated into 4 groups: (1) control; (2) APC i.v. only; (3) NIR light exposure only; (4) APC and NIR light (NIR-PIT). These were performed every week for up to 3 weeks. Rituximab-IR700 showed high tumor accumulation and high target-to-background ratio in vivo. Tumor growth was significantly inhibited by NIR-PIT in comparison with the other groups (p < 0.001 for both tumors), and survival was significantly prolonged in both tumors (p < 0.001 for Daudi tumors and p < 0.0001 for Ramos tumors vs other groups). More than half of tumors were cured with this single regimen of NIR-PIT. In conclusion, anti-CD20 rituximab-IR700 works as a highly effective APC for NIR-PIT against B-cell lymphoma.
| S-EPMC5067212 | biostudies-literature
Project description:Near Infrared-Photoimmunotherapy (NIR-PIT) is a new, highly selective tumor treatment that employs an antibody-photon absorber conjugate (APC). When the APC attaches to its target cell and is exposed to NIR light, highly selective cell killing is observed. NIR-PIT has been demonstrated with a limited number of antibodies. Mesothelin is overexpressed in several malignancies and is emerging as a therapeutic target. A recently humanized antibody (hYP218) has been generated against mesothelin that demonstrates high affinity binding. Here, we describe the efficacy of NIR-PIT, using hYP218 as the antibody within the APC to target a mesothelin expressing A431/H9 cell. The hYP218 antibody was conjugated to a photo-absorber, IR700 and incubated with the cells. The hYP218-IR700 showed specific binding to cells and cell-specific killing was observed in vitro. After implanting A431/H9 cells in an athymic nude mouse, tumor-bearing mice were treated with the following regimen of NIR-PIT; 100 ?g of hYP218-IR700 i.v., NIR light was administered at 50 J/cm2 on day 1 after injection and 100 J/cm2 of light on day 2 after injection. The hYP218-IR700 showed high tumor accumulation and a high tumor-background ratio (TBR). Tumor growth was significantly inhibited by NIR-PIT treatment compared with the other control groups (p < 0.001), and significantly prolonged survival (p < 0.0001 vs other groups). Thus, the new anti-mesothelin antibody, hYP218, is suitable as an antibody-drug conjugate for NIR-PIT. Furthermore, NIR-PIT with hYP218-IR700 is a promising candidate for the treatment of mesothelin-expressing tumors that could be readily translated to humans.
| S-EPMC5029632 | biostudies-literature
Project description:Cancer treatment has been founded traditionally on the three approaches of surgery, radiation, and chemotherapy with the latter recognized as the obvious systemic treatment approach applicable to disease that has spread. Although significant progress has been made over nearly 100 years of developing systemic treatments, it remains clear that use of the toxic agents involved is a two-edged sword with normal organ toxicities always needing to be balanced with and against administration of relevant therapeutic doses. With the advent of monoclonal antibodies targeted against tumor-associated antigens that could be used as carriers of potently toxic chemotherapy drugs, it was thought that such antibody-drug conjugates (ADCs) could engender the answer to the toxicity/therapeutic equation by shifting the equation more toward beneficial therapeutic efficacy. However, over 40 or so years, antibody-drug conjugates have not significantly affected the toxicity/therapy balance paradigm in most cancer indications, especially in solid tumors. Ideally, a further step may be required in that a non-tumor-targeted antibody-drug conjugate should be essentially nontoxic in its native administered form, with toxic effects unleashed only at the site of targeted tumors. A new approach that employs this principle is the use of an antibody-drug conjugate that is essentially nontoxic to normal tissues by virtue of requiring an extra step of light activation to become potent. We describe the preclinical data and first clinical results gained over the past few years by use of antibody-drug conjugates wherein the drug comprises a near-infrared photoactivatable dye delivered to tumors by a monoclonal antibody and is subsequently activated to a toxic entity solely at sites of tumors.
| S-EPMC7414968 | biostudies-literature
Project description:The bones are a common site for metastasis arising from solid tumors such as breast and prostate cancer. Chemotherapy, including immunotherapy, is rarely curative. Radiotherapy with pain palliation can temporize bone metastases but is generally considered a short-term solution and retreatment is difficult. Surgery is often necessary, yet recovery times might exceed life expectancy. Therefore, there is a need to develop new approaches to bone metastases that are effective but minimally invasive. Near-infrared photoimmunotherapy (NIR-PIT) uses antibodies labeled with IRDye700DX (IR700) which is activated by NIR light, resulting in rapid cell membrane damage and immunogenic cell death. NIR-PIT using an anti-epidermal growth factor receptor (EGFR) antibody-IR700 conjugate in patients with recurrent head and neck cancer received qualified approval in Japan in 2020 and is now widely used there. However, no bone metastases have yet been treated. In this study, the efficacy of NIR-PIT for bone metastases was investigated using a bone metastases mouse model successfully established by caudal artery injection of a human triple-negative breast cancer cell line, MDAMB468-GFP/luc. The bone metastatic lesions were treated with NIR-PIT using the anti-EGFR antibody, panitumumab-IR700 conjugate. Bioluminescence imaging and histological evaluation showed that EGFR-targeted NIR-PIT has a therapeutic effect on bone metastatic lesions in mice. In addition, micro-CT showed that repeated NIR-PIT led to repair of metastasis-induced bone destruction and restored bone cortex continuity consistent with healing. These data suggest that NIR-PIT has the potential for clinical application in the treatment of bone metastases.
| S-EPMC10024949 | biostudies-literature