Article
Oncology
Jiefu Jin, James D. Barnett, Balaji Krishnamachary, Yelena Mironchik, Catherine K. Luo, Hisataka Kobayashi, Zaver M. Bhujwalla
Summary: Photoimmunotherapy (PIT), using an Ab conjugated to the near infrared dye IRDye700DX, has achieved significant success in specifically eliminating cells. Fibroblast activation protein alpha (FAP-alpha) is an important target in cancer as it is expressed by cancer-associated fibroblasts (CAFs) and some cancer cells, playing a protumorigenic and immune suppressive role. In this study, FAP-alpha was found to be increased in invasive breast cancer tissue and in fibroblasts cocultured with cancer cells. By engineering cancer cells and fibroblasts to overexpress FAP-alpha, a specific Ab conjugate called FAP-alpha-IR700 was developed. FAP-alpha-IR700-PIT demonstrated effective killing of FAP-alpha expressing cells in engineered cancer cells and patient-derived CAFs, suggesting it as a promising strategy to eliminate FAP-alpha(+) CAFs.
Article
Medicine, Research & Experimental
Yifan Liu, Yansha Sun, Peng Wang, Songling Li, Yiwei Dong, Min Zhou, Bizhi Shi, Hua Jiang, Ruixin Sun, Zonghai Li
Summary: In this study, the combined antitumor activity of FAP-targeted and CLDN18.2-targeted CAR-T cells against PDAC was explored. The results showed that prior infusion of FAP-targeted CAR-T cells could eliminate CAFs and enhance the anti-PDAC efficacy of subsequently infused CLDN18.2-targeted CAR-T cells. Moreover, FAP-targeted CAR-T cells could suppress the recruitment of MDSCs and promote the survival of CD8(+) T cells and CAR-T cells in tumor tissue.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Ryoichi Katsube, Kazuhiro Noma, Toshiaki Ohara, Noriyuki Nishiwaki, Teruki Kobayashi, Satoshi Komoto, Hiroaki Sato, Hajime Kashima, Takuya Kato, Satoru Kikuchi, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Hisataka Kobayashi, Toshiyoshi Fujiwara
Summary: The study demonstrated that CAFs contribute to chemoradiotherapy resistance and drug resistance in cancer cells, but this resistance can be rescued by eliminating CAF stimulation.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Kohei Matsuoka, Mizuki Yamada, Mitsuo Sato, Kazuhide Sato
Summary: The conventional treatment for thoracic tumors includes surgery, drugs, radiation, and immunotherapy. Recently, near-infrared photoimmunotherapy (NIR-PIT) has emerged as a promising therapeutic approach for thoracic tumors. By targeting different antigens, NIR-PIT can be applied to any desired target.
Review
Chemistry, Physical
Dao Shi, Nan Wang, Jie Zhang, Xi Hu, Qiyue Wang, Ruixue Xiao, Baoyue Ding, Fangyuan Li, Daishun Ling
Summary: Photoimmunotherapy is a promising therapeutic approach that combines phototherapy and immunotherapy to eliminate tumors and activate the host immune response. Tumor-responsive dynamic nanoassemblies play a crucial role in high-performance photoimmunotherapy, but the interaction between nanoassemblies and the tumor microenvironment is still not well understood. This review discusses the rational design, nano-bio interactions, and controllable functionalities of cutting-edge nanoassemblies for enhanced photoimmunotherapy, and emphasizes the synergistic mechanism between nanoassemblies-based photoimmunotherapy and immunomodulatory agents-mediated immunomodulation.
Article
Oncology
Susumu Yamashita, Miho Kojima, Nobuhiko Onda, Toshinori Yoshida, Makoto Shibutani
Summary: Near-infrared photoimmunotherapy (NIR-PIT) is a novel treatment for HER2-positive cancers, including breast cancer, using conjugates of antibody against overexpressed antigens and photoabsorber IRDye700DX. This study investigated the efficacy of HER2-targeted NIR-PIT using trastuzumab-IRDye700DX conjugate (Tra-IR700) in HER2-positive breast cancer. The results showed that NIR-PIT with Tra-IR700 induced a highly selective therapeutic effect in a HER2-positive breast cancer model.
Article
Oncology
Shunichi Taki, Kohei Matsuoka, Yuko Nishinaga, Kazuomi Takahashi, Hirotoshi Yasui, Chiaki Koike, Misae Shimizu, Mitsuo Sato, Kazuhide Sato
Summary: The study modified photoimmunotherapy by targeting PD-L1 to enhance anticancer immune system. The therapy showed limited effect on tumor cells in vitro but induced sufficient antitumor effects in vivo, mediated by the 'photoimmuno' effect and antitumor immunity augmentation. The local PD-L1-targeted NIR-PIT enhanced the antitumor immune reaction through direct photonecrotic effect, providing an alternative approach to targeted cancer immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Taiki Moriya, Mayuko Hashimoto, Hina Matsushita, Shion Masuyama, Rina Yoshida, Ryuhei Okada, Aki Furusawa, Daiki Fujimura, Hiroaki Wakiyama, Takuya Kato, Peter L. Choyke, Yutaka Kusumoto, Tatyana Chtanova, Hisataka Kobayashi, Michio Tomura
Summary: Near-infrared photoimmunotherapy (NIR-PIT) selectively kills tumor cells and induces a systemic anti-tumor immune response. This study shows that NIR-PIT enhances migration of tumor-infiltrating dendritic cells (Ti-DCs) to draining lymph nodes (dLNs) via ATP-P2X7 receptor and G alpha i protein-coupled receptor signaling pathways, promoting tumor antigen presentation and the induction of anti-tumor T cells in dLNs.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Oncology
Meihua Chen, Ling Xiao, Hongyuan Jia, Shubin Wang, Xiao Jiang, Xudan Lei, Qiming Zhai, Jinyi Lang
Summary: This study found that a combination of stereotactic ablation radiotherapy (SABR) and a cancer vaccine targeting fibroblast activation protein-alpha (FAP alpha) can suppress established tumor growth and impede potential metastasis. The combination therapy showed promising results against poorly immunogenic metastatic cancer.
RADIOTHERAPY AND ONCOLOGY
(2023)
Article
Medicine, Research & Experimental
Fuyuki F. Inagaki, Hiroaki Wakiyama, Aki Furusawa, Ryuhei Okada, Takuya Kato, Daiki Fujimura, Shuhei Okuyama, Hiroshi Fukushima, Seiichiro Takao, Peter L. Choyke, Hisataka Kobayashi
Summary: Bones are a common site for metastasis from solid tumors, and current treatments are not curative. Near-infrared photoimmunotherapy (NIR-PIT), which uses antibodies labeled with IRDye700DX (IR700) activated by NIR light, has shown success in treating head and neck cancer but has not been tested on bone metastases. This study investigated the efficacy of EGFR-targeted NIR-PIT on bone metastatic lesions using a mouse model and found that it had a therapeutic effect and could repair metastasis-induced bone destruction.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Oncology
Hiroshi Fukushima, Baris Turkbey, Peter A. Pinto, Aki Furusawa, Peter L. Choyke, Hisataka Kobayashi
Summary: Near-infrared photoimmunotherapy (NIR-PIT) is a novel molecularly-targeted therapy that selectively kills cancer cells by injecting an antibody-photoabsorber conjugate (APC) that binds to cancer cells, followed by the application of NIR light. NIR-PIT can selectively kill cancer cells without harming normal tissues and activates anti-cancer immunity.
Article
Chemistry, Physical
Yao Huang, Tingting Peng, Yangyan Chen, Fapeng Zhang, Wanshan Hu, XinYi Gao, Hongyu Chen, Ping Tang, Chuanbin Wu, Xin Pan
Summary: This study developed an oxygen reservoir-irrigated photodynamic therapy (PDT) that integrates oxygen supply, oxygen economizing, and oxygen infiltration. By modulating tumor oxygenation and permeability, it achieves complete eradication of primary melanoma and stimulates immunogenic cell death.
Article
Chemistry, Physical
Yao Huang, Tingting Peng, Yangyan Chen, Fapeng Zhang, Wanshan Hu, XinYi Gao, Hongyu Chen, Ping Tang, Chuanbin Wu, Xin Pan
Summary: An oxygen reservoir-irrigated photodynamic therapy has been developed to improve the efficacy of tumor treatment by considering oxygen supply, economizing, and infiltration. This therapy effectively reduces tumor hypoxia, promotes immunogenic cell death, and enhances the antitumor effects when combined with checkpoint-blockade inhibitors.
Article
Multidisciplinary Sciences
Hiroaki Sato, Kazuhiro Noma, Toshiaki Ohara, Kento Kawasaki, Masaaki Akai, Teruki Kobayashi, Noriyuki Nishiwaki, Toru Narusaka, Satoshi Komoto, Hajime Kashima, Yuki Katsura, Takuya Kato, Satoru Kikuchi, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Hisataka Kobayashi, Toshiyoshi Fujiwara
Summary: This study investigated the efficacy of dual-targeted near-infrared photoimmunotherapy (NIR-PIT) as a therapeutic strategy for cancer treatment. The results showed that dual-targeted NIR-PIT had specific therapeutic effects on both cancer cells and cancer-associated fibroblasts (CAFs), suppressing tumor growth in vivo. Therefore, dual-targeted NIR-PIT may be a promising therapeutic strategy for cancer treatment.
SCIENTIFIC REPORTS
(2022)
Review
Medicine, General & Internal
Yasuhiro Maruoka, Hiroaki Wakiyama, Peter L. Choyke, Hisataka Kobayashi
Summary: Near-infrared photoimmunotherapy (NIR-PIT) is a highly-selective cancer treatment using a photoabsorbing dye, currently undergoing global phase III clinical trials and conditionally approved in Japan. In addition to rapid, selective cancer cell death, it also stimulates anti-tumour immunity and may have improved results in combination with immune-checkpoint inhibitors.
Article
Gastroenterology & Hepatology
Kazuyuki Matsumoto, Toshiaki Ohara, Masayoshi Fujisawa, Akinobu Takaki, Masahiro Takahara, Hironari Kato, Ryuichi Yoshida, Yuzo Umeda, Takahito Yagi, Akihiro Matsukawa, Hiroyuki Okada
Summary: This study evaluated whether biopsy specimens could predict the positive status of PD-L1 in surgically resected tissue. The results showed a substantial positive and high negative concordance rates between biopsy samples and surgically resected tissues in terms of PD-L1 expression.
JOURNAL OF GASTROINTESTINAL SURGERY
(2022)
Article
Environmental Sciences
Toshiaki Ohara, Ken Yuasa, Kentaro Kimura, Shiho Komaki, Yuta Nishina, Akihiro Matsukawa
Summary: A mechanical rolling compression method with high dehydration ability was developed to reduce the moisture content of plant biomass for use as fuel. The squeezed liquid contained water-soluble lignin and exhibited antiviral effects. This novel method has the potential to alter fossil fuels.
JOURNAL OF MATERIAL CYCLES AND WASTE MANAGEMENT
(2023)
Article
Oncology
Yoshinori Kajiwara, Hiroshi Tazawa, Motohiko Yamada, Nobuhiko Kanaya, Takuro Fushimi, Satoru Kikuchi, Shinji Kuroda, Toshiaki Ohara, Kazuhiro Noma, Ryuichi Yoshida, Yuzo Umeda, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara
Summary: GEM-resistant PDAC cells express high levels of PD-L1 and produce high levels of GM-CSF, leading to immunosuppressive tumor microenvironment and accumulation of MDSCs. OBP-702 can effectively inhibit the growth of GEM-resistant PDAC tumors and enhance the anti-tumor efficacy of PD-L1 blockade.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Gastroenterology & Hepatology
Kazutaka Takahashi, Kunitoshi Shigeyasu, Yoshitaka Kondo, Kazuyoshi Gotoh, Shuya Yano, Yuzo Umeda, Toshihiro Inokuchi, Caiming Xu, Kazuhiro Yoshida, Hibiki Umeda, Toshiaki Takahashi, Sho Takeda, Ryuichi Yoshida, Fuminori Teraishi, Hiroyuki Kishimoto, Yoshiko Mori, Kazuhiro Noma, Yoshinaga Okugawa, Sakiko Hiraoka, Hiroyuki Michiue, Hiroshi Tazawa, Osamu Matsushita, Ajay Goel, Toshiyoshi Fujiwara
Summary: Ulcerative colitis (UC) can lead to colitis-associated colorectal neoplasm (CAN), and ADAR1 may be involved in the development of CAN in UC. Assessing ADAR1 expression in the rectum of MES0 UC patients can evaluate the risk of CAN and reduce the physical burden on patients. RNA editing may be involved in UC carcinogenesis and can be used for the prevention and treatment of CAN in UC.
JOURNAL OF CROHNS & COLITIS
(2023)
Article
Oncology
Yuze Wang, Toshiaki Ohara, Yuehua Chen, Yusuke Hamada, Chunning Li, Masayoshi Fujisawa, Teizo Yoshimura, Akihiro Matsukawa
Summary: Excess iron is a risk factor for carcinogenesis, but iron chelators have not been successfully used to treat cancer patients. This study found that iron chelators could have therapeutic potential for triple-negative breast cancer (TNBC). The iron chelator Deferasirox suppressed the growth of TNBC cells and reduced lung metastases in mouse models. Highly metastatic TNBC cells have limited iron metabolism and are more susceptible to iron chelators.
Article
Oncology
Noriyuki Nishiwaki, Kazuhiro Noma, Toshiaki Ohara, Tomoyoshi Kunitomo, Kento Kawasaki, Masaaki Akai, Teruki Kobayashi, Toru Narusaka, Hajime Kashima, Hiroaki Sato, Satoshi Komoto, Takuya Kato, Naoaki Maeda, Satoru Kikuchi, Shunsuke Tanabe, Hiroshi Tazawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara
Summary: Cancer-associated fibroblasts (CAFs) play a critical role in tumor progression by inducing tumor immunosuppression via IL-6. IL-6 induces tumor immunosuppression by enhancing glucose uptake by cancer cells and competing for glucose with immune cells. Anti-IL-6 receptor antibody could overcome tumor immunosuppression and inhibit tumor progression.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Tong Gao, Xu Yang, Masayoshi Fujisawa, Toshiaki Ohara, Tianyi Wang, Nahoko Tomonobu, Masakiyo Sakaguchi, Teizo Yoshimura, Akihiro Matsukawa
Summary: The downregulation of SPRED2 promotes EMT and stemness in hepatocellular carcinoma through the activation of the ERK1/2 pathway, leading to more malignant phenotypes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Satoshi Komoto, Kazuhiro Noma, Takuya Kato, Teruki Kobayashi, Noriyuki Nishiwaki, Toru Narusaka, Hiroaki Sato, Yuki Katsura, Hajime Kashima, Satoru Kikuchi, Toshiaki Ohara, Hiroshi Tazawa, Toshiyoshi Fujiwara
Summary: Esophageal cancer patients who undergo esophagectomy with chemoradiotherapy have a low 5-year survival rate of 32.4%. This is due to the low response rate to preoperative chemotherapy or radiotherapy. The study found that low-dose chemotherapy or radiotherapy caused malignant phenotypic changes in normal fibroblasts, and radiotherapy-resistant fibroblasts increased the number of tumors in peritoneal-disseminated tumor models. Conventional cancer therapy can have anti-therapeutic effects by activating fibroblasts, highlighting the importance of selecting appropriate modalities for esophageal cancer treatment to avoid tumor resistance.
Article
Oncology
Kento Kawasaki, Kazuhiro Noma, Takuya Kato, Toshiaki Ohara, Shunsuke Tanabe, Yasushige Takeda, Hijiri Matsumoto, Seitaro Nishimura, Tomoyoshi Kunitomo, Masaaki Akai, Teruki Kobayashi, Noriyuki Nishiwaki, Hajime Kashima, Naoaki Maeda, Satoru Kikuchi, Hiroshi Tazawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara
Summary: The PD-1/PD-L1 axis plays a crucial role in tumor immunosuppression, and the mutual enhancement of PD-L1 expression between cancer cells and CAFs leads to tumor immunosuppression. PD-L1-expressing CAFs may be promising targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Oncology
Masashi Yoshimoto, Shunsuke Kagawa, Hiroki Kajioka, Atsuki Taniguchi, Shinji Kuroda, Satoru Kikuchi, Yoshihiko Kakiuchi, Tomohiko Yagi, Shohei Nogi, Fuminori Teraishi, Kunitoshi Shigeyasu, Ryuichi Yoshida, Yuzo Umeda, Kazuhiro Noma, Hiroshi Tazawa
Summary: This study clarifies the involvement of neutrophil extracellular traps (NETs) in cancer metastasis, specifically in intrahepatic cholangiocarcinoma (iCCA). The study demonstrates that the binding of platelets to iCCA cells promotes the induction of NETs, and inhibiting platelet activation and NET production could prevent micrometastases of iCCA cells.
Review
Pharmacology & Pharmacy
Yoshihiko Kakiuchi, Shinji Kuroda, Nobuhiko Kanaya, Shunsuke Kagawa, Hiroshi Tazawa, Toshiyoshi Fujiwara
Summary: This article introduces the important role of cell-derived nanovesicles, exosomes, in cell-to-cell communication. It also discusses how combining exosomes with existing therapeutic agents can enhance therapeutic effects and trigger immunogenic cell death. Combining oncolytic viruses with exosomes can overcome limitations of the viruses and improve their anti-tumor effects. The use of exosomes as a novel therapy shows great potential for enhancing therapeutic efficacy and overcoming disadvantages in cancer treatments.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Article
Infectious Diseases
Yuki Shinoda-Ito, Kazuhiro Omori, Takashi Ito, Masaaki Nakayama, Atsushi Ikeda, Masahiro Ito, Toshiaki Ohara, Shogo Takashiba
Summary: This study evaluated the inhibitory effects of super-polyphenols (SPs) on the cariogenic bacterium Streptococcus mutans. The results showed that certain types of SPs could effectively inhibit bacterial growth and have the potential to control oral bacterial infections.