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Cancers
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Near-Infrared Photoimmunotherapy for Cancer Treatment
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Near-Infrared Photoimmunotherapy for Cancer Treatment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (10 April 2024) | Viewed by 11227

Special Issue Editor

Dr. Hisataka Kobayashi

E-Mail Website
Guest Editor
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Interests: molecular imaging; photo-immunotherapy; molecular probe chemistry

Special Issue Information

Dear Colleagues,

Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed, molecularly targeted cancer phototherapy involving conjugating a near-infrared silica-phthalocyanine dye, IRDye700DX (IR700), to monoclonal-antibody (mAb)-targeting cell-surface molecules. NIR-PIT targeting EGFR using cetuximab-IR700 conjugates is now undergoing a global Phase 3 clinical trial in late-stage head and neck squamous cell cancer patients, and was approved for clinical use under health insurance in Japan in September 2020. NIR-PIT is different from conventional photodynamic therapy (PDT) in photochemistry and cytotoxic mechanisms, resulting in a superior safety profile in preclinical and clinical studies.

Inviting contributions：This Special Issue welcomes research articles and review papers focused on a wide scope of NIR-PIT-related science, from basic photochemistry to preclinical and clinical NIR-PIT studies.

Dr. Hisataka Kobayashi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • NIR-PIT
  • phototherapy
  • monoclonal antibody
  • imaging biomarker
  • immunotherapy

Published Papers (5 papers)

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Research

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12 pages, 2293 KiB  
Article
Eligibility for Photoimmunotherapy in Patients with Unresectable Advanced or Recurrent Head and Neck Cancer and Changes before and after Systemic Therapy
by Takeshi Shinozaki, Kazuto Matsuura, Wataru Okano, Toshifumi Tomioka, Yukio Nishiya, Michiko Machida and Ryuichi Hayashi
Cancers 2023, 15(15), 3795; https://doi.org/10.3390/cancers15153795 - 26 Jul 2023
Cited by 2 | Viewed by 1111
Abstract
Photoimmunotherapy is a novel cancer treatment that recently became covered by national health insurance in Japan, but treatment decision-making remains challenging for unresectable advanced or recurrent head and neck cancer. We aimed to clarify the characteristics of patients for whom photoimmunotherapy was indicated [...] Read more.
Photoimmunotherapy is a novel cancer treatment that recently became covered by national health insurance in Japan, but treatment decision-making remains challenging for unresectable advanced or recurrent head and neck cancer. We aimed to clarify the characteristics of patients for whom photoimmunotherapy was indicated by a retrospective chart review. Patients aged ≥20 years diagnosed with advanced or recurrent head and neck cancer who started receiving systemic therapy at the National Cancer Center Hospital East from January 2016 through December 2020 were retrospectively analyzed. Before and after first-line systemic therapy, patients were classified into 3 groups according to eligibility for photoimmunotherapy: eligible, potentially eligible, and ineligible. In total, of 246 patients evaluated—194 after exclusions were analyzed—108 were deemed ineligible for treatment. Of the remaining 86 patients, 8 were considered potentially eligible and 9 eligible. Of the nine eligible patients, four became ineligible after receiving first-line systemic therapy due to disease progression. Our results suggest that the indication of photoimmunotherapy should be considered before, during, and after systemic therapy for unresectable locally advanced or recurrent head and neck cancer. Full article
(This article belongs to the Special Issue Near-Infrared Photoimmunotherapy for Cancer Treatment)
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13 pages, 28836 KiB  
Article
In Vitro Comparative Study of Near-Infrared Photoimmunotherapy and Photodynamic Therapy
by Susumu Yamashita, Miho Kojima, Nobuhiko Onda and Makoto Shibutani
Cancers 2023, 15(13), 3400; https://doi.org/10.3390/cancers15133400 - 28 Jun 2023
Cited by 1 | Viewed by 1463
Abstract
Near-infrared photoimmunotherapy (NIR-PIT) is a new phototherapy that utilizes a monoclonal antibody (mAb) against cancer antigens and a phthalocyanine dye, IRDye700DX (IR700) conjugate (mAb-IR700). Photodynamic therapy (PDT) is a combination therapy that utilizes photoreactive agents and light irradiation as well as NIR-PIT. In [...] Read more.
Near-infrared photoimmunotherapy (NIR-PIT) is a new phototherapy that utilizes a monoclonal antibody (mAb) against cancer antigens and a phthalocyanine dye, IRDye700DX (IR700) conjugate (mAb-IR700). Photodynamic therapy (PDT) is a combination therapy that utilizes photoreactive agents and light irradiation as well as NIR-PIT. In the present study, we compared these therapies in vitro. The characterization of cellular binding/uptake specificity and cytotoxicity were examined using two mAb-IR700 forms and a conventional PDT agent, talaporfin sodium, in three cell lines. As designed, mAb-IR700 had high molecular selectivity and visualized target molecule-positive cells at the lowest concentration examined. NIR-PIT induced necrosis and damage-associated molecular patterns (DAMPs), a surrogate maker of immunogenic cell death. In contrast, talaporfin sodium was taken up by cells regardless of cell type, and its uptake was enhanced in a concentration-dependent manner. PDT induced cell death, with the pattern of cell death shifting from apoptosis to necrosis depending on the concentration of the photosensitizer. Induction of DAMPs was observed at the highest concentration, but their sensitivity differed among cell lines. Overall, our data suggest that molecule-specific NIR-PIT may have potential advantages compared with PDT in terms of the efficiency of tumor visualization and induction of DAMPs. Full article
(This article belongs to the Special Issue Near-Infrared Photoimmunotherapy for Cancer Treatment)
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13 pages, 3769 KiB  
Article
Optimal Light Dose for hEGFR-Targeted Near-Infrared Photoimmunotherapy
by Hideyuki Furumoto, Ryuhei Okada, Takuya Kato, Hiroaki Wakiyama, Fuyuki Inagaki, Hiroshi Fukushima, Shuhei Okuyama, Aki Furusawa, Peter L. Choyke and Hisataka Kobayashi
Cancers 2022, 14(16), 4042; https://doi.org/10.3390/cancers14164042 - 22 Aug 2022
Cited by 2 | Viewed by 1912
Abstract
Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer therapy that targets cancer cells using a monoclonal antibody-photon absorber conjugate (APC) that is bound to the target cell surface. Subsequent application of low levels of NIR light results in immediate cancer cell death. The [...] Read more.
Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer therapy that targets cancer cells using a monoclonal antibody-photon absorber conjugate (APC) that is bound to the target cell surface. Subsequent application of low levels of NIR light results in immediate cancer cell death. The anti-tumor effect of NIR-PIT in immunocompromised mice depends on immediate cancer cell death; therefore, the efficacy increases in a light-dose-dependent manner. However, NIR-PIT also induces a strong anti-tumor immune activation in immunocompetent mice that begins soon after therapy. Thus, it may be possible to reduce the light dose, which might otherwise cause local edema while maintaining therapeutic efficacy. In this study, we determined the optimal dose of NIR light in NIR-PIT based on a comparison of the therapeutic and adverse effects. Either one of two monoclonal antibodies (mAbs) against human epidermal growth factor receptor (hEGFR), Cetuximab or Panitumumab, were conjugated with a photo-absorbing chemical, IRDye700DX (IR700), and then injected in hEGFR-expressing mEERL (mEERL-hEGFR) tumor-bearing C57BL/6 immunocompetent mice or A431-GFP-luc tumor-bearing athymic immunocompromised mice. NIR light was varied between 0 to 100 J/cm2 one day after administration of APC. In an immunocompromised mouse model, tumor growth was inhibited in a light-dose-dependent manner, yet extensive local edema and weight loss were observed at 100 J/cm2. On the other hand, in an immunocompetent mouse model using the mEERL-hEGFR cell line, maximal tumor response was achieved at 50 J/cm2, with a commensurate decrease in local edema. In this study, we show that a relatively low dose of NIR light is sufficient in an immunocompetent mouse model and avoids side effects seen with higher light doses required in immunocompetent mice. Thus, light dosing can be optimized in NIR-PIT based on the expected immune response. Full article
(This article belongs to the Special Issue Near-Infrared Photoimmunotherapy for Cancer Treatment)
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15 pages, 3102 KiB  
Article
Phototheranostics of Splenic Myeloid-Derived Suppressor Cells and Its Impact on Spleen Metabolism in Tumor-Bearing Mice
by James D. Barnett, Jiefu Jin, Marie-France Penet, Hisataka Kobayashi and Zaver M. Bhujwalla
Cancers 2022, 14(15), 3578; https://doi.org/10.3390/cancers14153578 - 22 Jul 2022
Cited by 6 | Viewed by 2682
Abstract
(1) Background: MDSCs play an active role in the immune surveillance escape of cancer cells. Because MDSCs in mice are CD11b+Gr1+, near-infrared photoimmunotherapy (NIR-PIT) using the NIR dye IR700 conjugated to an MDSC-binding antibody provides an opportunity for targeted [...] Read more.
(1) Background: MDSCs play an active role in the immune surveillance escape of cancer cells. Because MDSCs in mice are CD11b+Gr1+, near-infrared photoimmunotherapy (NIR-PIT) using the NIR dye IR700 conjugated to an MDSC-binding antibody provides an opportunity for targeted elimination of MDSCs. (2) Methods: The efficacy of Gr1-IR700-mediated NIR-PIT was evaluated in vitro using magnetically separated CD11b+Gr1+ MDSCs from spleens of 4T1-luc tumor-bearing (TB) mice. For in vivo evaluation, spleens of Gr1-IR700-injected 4T1-luc TB mice were irradiated with NIR light, and splenocyte viability was determined using CCK-8 assays. Metabolic profiling of NIR-PIT-irradiated spleens was performed using 1H MRS. (3) Results: Flow cytometric analysis confirmed a ten-fold increase in splenic MDSCs in 4T1-luc TB mice. Gr1-IR700-mediated NIR-PIT eliminated tumor-induced splenic MDSCs in culture. Ex vivo fluorescence imaging revealed an 8- and 9-fold increase in mean fluorescence intensity (MFI) in the spleen and lungs of Gr1-IR700-injected compared to IgG-IR700-injected TB mice. Splenocytes from Gr1-IR700-injected TB mice exposed in vivo to NIR-PIT demonstrated significantly lower viability compared to no light exposure or untreated control groups. Significant metabolic changes were observed in spleens following NIR-PIT. (4) Conclusions: Our data confirm the ability of NIR-PIT to eliminate splenic MDSCs, identifying its potential to eliminate MDSCs in tumors to reduce immune suppression. The metabolic changes observed may identify potential biomarkers of splenic MDSC depletion as well as potential metabolic targets of MDSCs. Full article
(This article belongs to the Special Issue Near-Infrared Photoimmunotherapy for Cancer Treatment)
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Review

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21 pages, 1374 KiB  
Review
Near-Infrared Photoimmunotherapy (NIR-PIT) in Urologic Cancers
by Hiroshi Fukushima, Baris Turkbey, Peter A. Pinto, Aki Furusawa, Peter L. Choyke and Hisataka Kobayashi
Cancers 2022, 14(12), 2996; https://doi.org/10.3390/cancers14122996 - 17 Jun 2022
Cited by 8 | Viewed by 2903
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Near-Infrared Photoimmunotherapy for Cancer Treatment)
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