CT detection of primary and metastatic tumor and their treatment abscopal effect via radiation

• Project/Area Number: 17K10489
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Iwate Medical University
• Principal Investigator: Harada Satoshi 岩手医科大学, 医学部, 講師 (20244931)
• Project Period (FY): 2017-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: Radiation / Durg Delivery System / Particle imaging / microprobe imaging / immunotherapy / Drug delivery system / Abscopal effect / Hyaluronic acid / Immunotherapy / Particle / Microprobe / Radiaton / Drug Delivery System / Prtoamine / DC priming / PIXE

Outline of Final Research Achievements

We aimed to image and treat the primary tumor by immunogenic cell death (ICD), and metastatic treatment through abscopal effect using particles that release liposome-protamine-hyaluronic acid nanoparticles (LPH-NP) in response to radiation, in two radiation sessions.
The accumulation of particles via antigen-antibody of VEGRF1/2 allowed us to image Primary tumor and metastases. First radiation localized anti-CD47 si-RNA, anti-PD-L1-Ab and P-selectin. Second radiation session localized HMGB-1, ATP, and anti-CD47 si-RNA. These treatments facilitated attacking tumor and metastasis by CD8+-T-cell, which resulted in increasing the antitumor effect and reduced metastasis.

Academic Significance and Societal Importance of the Research Achievements

学術的意義：放射線に、ドラッグデリバリーシステムという新たな役割を与える。パーティクルを使用した放射線診断と放射線治療の同時施行を可能にする。
社会的意義：パーテイクルによる放射線治療効果増強と副作用軽減を同時に行うことで、高齢化社会の癌治療に貢献する。

Research Products

• [Journal Article] Treatment of primary and metastatic tumor through cancer immunotherapy and abscopal effect by targeted antigen-capturing nanoparticles with programmed death-1 blockade (2023)
  • Author(s): Satoshi Harada, Takahiro Sato
  • Journal Title: International Journal of PIXE Volume: 28 Issue: 03n04 Pages: 69-76
  • DOI: 10.1142/s0129083518500158
  • Peer Reviewed
• [Journal Article] Inhibition of metastasis using particles that release chitosan upon radiation: A preliminary study (2023)
  • Author(s): Satoshi Harada, Takahiro Sato
  • Journal Title: International Journal of PIXE Volume: 29 Issue: 01n02 Pages: 1-6
  • DOI: 10.1142/s0129083519500104
  • Peer Reviewed
• [Journal Article] Inhibition of metastasis using particles that release chitosan upon radiation (2021)
  • Author(s): Satoshi Harada, Takahiro Sato
  • Journal Title: International Journal of PIXE Volume: 29 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Treatment of primary and metastatic tumors through cancer immunotherapy and abscopal effect by targeted antigen-capturing nanoparticles with programmed death-1 blockade (2020)
  • Author(s): Satoshi Harada, , Takafumi Segawa Shigeru Ehara, Takahiro Sato
  • Journal Title: International Journal of PIXE Volume: 28 Pages: 69-76
  • Peer Reviewed
• [Journal Article] Delivery and Effectiveness of Carboplatin via Targeted Delivery Compared to Passive Accumulation of Intravenously Injected Particles Releasing Carboplatin upon Irradiation (2020)
  • Author(s): Takafumi Segawa, Satoshi Harada, Takahiro Sato, Shigeru Ehara
  • Journal Title: RADIATION RESEARCH Volume: 193 Issue: 3 Pages: 263-263
  • DOI: 10.1667/rr15357.1
  • Peer Reviewed
• [Journal Article] Encapsulated protamine-hyaluronic acid particles for targeting carboplatin directed by radiation (2018)
  • Author(s): T. Segawa, S. Harada, S. Ehara, K. Ishii, K. Sera, S. Goto
  • Journal Title: International Journal of PIXE, Volume: 27 Issue: 01n02 Pages: 37-42
  • DOI: 10.1142/s0129083518500043
  • Peer Reviewed
• [Journal Article] Encapsulated protamine-hyaluronic acid particles for targeting carboplatin directed by radiation. (2018)
  • Author(s): Takashi Segawa, Satoshi Harada, Shigeru Ehara, Keizo Ishii, Takahiro Sato, Koichiro Sera, Shyoko Goto
  • Journal Title: International Journal of PIXE Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Targeted pubic neoantigen immunotherapy using encapsulated nanoparticles, directed by radiation (2023)
  • Author(s): Satoshi Harada
  • Organizer: ASTRO's 65th Annual Meeting
  • Int'l Joint Research
• [Presentation] Targeted theranostic nanomedicine. using targeted CT-imagable particles that release bispecific antibody IMC-KrasG12D and KrasG12D neoantigen, directed by two radiation sessions. (2023)
  • Author(s): Satoshi Harada
  • Organizer: Annual Meeting of Radiologyical Society of North America 2023
  • Int'l Joint Research
• [Presentation] Imaging of Primary and Metastatic Tumors Treated with Radiotherapy -Directed Antigen Capturing Nanoparticles, reducing metastasis seeding and colonization, under PDL-1 Blockade. (2022)
  • Author(s): Satoshi Harada, Takahiro Satoh
  • Organizer: 64th ASTRO's Annual Meeting
  • Int'l Joint Research
• [Presentation] Imaging and Treatment of Primary and Metastatic Tumors Through Immunotherapy and the Abscopal Effect Characterized by Reduced Circulating Tumor Cells, Cluster Formation, and Tumor Extravasation Via Administration of Radiation-Targeted Particles (2022)
  • Author(s): Satoshi Harada, Takahiro Satoh
  • Organizer: 第81回日本医学放射線学会総会
• [Presentation] Imaging of Primary and Metastatic Tumors Treated with Radiotherapy -Directed Antigen Capturing Nanoparticles (AC-NP), Dissciatoion of Circulating Tumor Cell (CTC)-Cluster and Their Reduced extravasation, underPDL-1 Blockade. (2021)
  • Author(s): Satoshi Harada, Takahiro Sato
  • Organizer: 63rd Annual Meeting of American Society of Therapeutic Radiation Oncology (ASTRO)
  • Int'l Joint Research
• [Presentation] Imaging and treatment of primary and metastatic tumors via abscopal immunotherapy involving reductions in circulating tumor cells (CTCs), CTC clusters, and their extravasation using targeted antigen-capturing nanoparticles containing Ezrin inhibitor and Ouabain directed by radiation. (2021)
  • Author(s): Satoshi Harada, Takahiro Sato,
  • Organizer: 107th Annual Meeting of Radiological Society of North America (RSNA)
  • Int'l Joint Research
• [Presentation] Imaging and Treatment of Primary and Metastatic Tumors, through Immunotherapy and Abscopal Effects with reduced Circulating-Tumor-Cells cluster-formation by Radiation-Targeted Particles (2021)
  • Author(s): Satoshi Harada, Takahiro Sato,
  • Organizer: 第81 回本医学放射線学会学術集会,
• [Presentation] Imaging and Treatment of Primary and Metastatic Tumors, through Immunotherapy and Abscopal Effects with Reduced Circulating-Tumor-Cells by Radiation-Targeted Particles. (2020)
  • Author(s): 原田 聡
  • Organizer: 第79回日本医学放射線学会総会
• [Presentation] Imaging of Primary and Metastatic Tumor and Their Treatment Via Cancer Immunotherapy, Abscopal Effects, and Dissociation of Circulating Tumor Cell (CTC)-Cluster, Using Radiotherapy-Directed Encapsulated Antigen-Capturing Nanoparticles Containing Na+/K+-ATPase Inhibitor. (2020)
  • Author(s): Satoshi Harada, Takahiro Sato,
  • Organizer: 62nd Annual Meeting of American Society for Radiation Oncoloty
  • Int'l Joint Research
• [Presentation] Imaging and treatment of primary and metastasized tumors through abscopal immunotherapy effects, and dissociation of circulating tumor cell-clusters using targeted antigen-capturing nanoparticles containing Ouabain, directed by radiation. (2020)
  • Author(s): Satoshi Harada, Takahiro Sato,
  • Organizer: 106th Scientific Assembly and Anuual Meeting of Radiological Society of North America
  • Int'l Joint Research
• [Presentation] Imaging of Primary and Metastatic Tumors and Their Treatment through via Cancer Immunotherapy, Abscopal Effects, and Reduction of Circulating Tumor Cells Using Radiotherapy-Directed Encapsulated Antigen-Capturing Nanoparticles containing Chitosan (2019)
  • Author(s): Satoshi Harada
  • Organizer: 2019 ASTRO Annual Meeting
  • Int'l Joint Research
• [Presentation] Imaging and treatment of primary and metastasized tumors through immunotherapy using targeted antigen-capturing nanoparticles with serum amyloid A1 along with radiation and PD-L1 blockade (2019)
  • Author(s): Satoshi Harada
  • Organizer: 105th Scientific Assembly and Annual meeting RSNA 2019
  • Int'l Joint Research
• [Presentation] Imaging of Primary and Metastatic Tumors and their Treatment through Abscopal Effects and Cancer Immunotherapy using Encapsulated, Radiotherapy-Directed Malemide-Antigen-Capturing Nanoparticles (2019)
  • Author(s): Satoshi Harada
  • Organizer: 第78回日本医学放射線学会総会
• [Presentation] Nanoparticle imaging and treatment of tumor, through macrophage-based therapy, by radiotherapy-targeted-switching of Tumor-Associated-Macrophages (TAM s) from M2 to M1 phenotype. (2018)
  • Author(s): Satoshi Harada
  • Organizer: 第77回日本医学放射線学会総会
• [Presentation] Imaging of Primary and Metastatic Tumors and their Treatment through Abscopal Effects and Cancer Immunotherapy using Encapsulated, Radiotherapy-Directed Antigen-Capturing Nanoparticles (2018)
  • Author(s): Satoshi Harada
  • Organizer: 56th Annual Meeting of the American Society for Radiation Oncology (ASTRO
  • Int'l Joint Research
• [Presentation] Imaging and treatment of primary and metastasized tumors through immunotherapy using targeted antigen-capturing nanoparticles with serum amyloid A1 along with radiation and PD-L1 blockade (2018)
  • Author(s): Satoshi Harada
  • Organizer: 104th Scientific Assembly and Annual Meeting of Radiological Society of North America (RSNA)
  • Int'l Joint Research
• [Presentation] Imaging of Primary and Metastatic Tumors and their Treatment through Abscopal Effects and Cancer Immunotherapy using Encapsulated, Radiotherapy-Directed Antigen-Capturing Nanoparticles (2018)
  • Author(s): Satoshi Harada , Takashi SeShigeru Ehara a, Takahiro Sato , Koichiro Sera, Shyoko Goto.
  • Organizer: 60th Annual Meeting of America Society of Radiation Oncology, 2018
  • Int'l Joint Research
• [Presentation] Nanoparticle imaging and treatment of primary and metastasized tumor through immunogenic cell death (ICD) and abscopal effect, respectively, by targeted Mertk inhibitor and PD-1 blockade via radiotherapy . (2017)
  • Author(s): Satoshi Harada , Takashi Segawa, Shigeru Ehara a,, Takahiro Sato , Koichiro Sera, Shyoko Goto.
  • Organizer: 第76回日本医学放射線学会総会
• [Presentation] Encapsulated protamine-hyaluronic acid particles for targeting carboplatin directed by radiation. (2017)
  • Author(s): Satoshi Harada , Takashi SeShigeru Ehara a, Takahiro Sato , Koichiro Sera, Shyoko Goto.
  • Organizer: 第33回PIXE シンポジウム京都
• [Presentation] Imaging of primary tumor and metastases and their treatment through targeted macrophage therapy, using encapsulated nanoparticles directed by radiotherapy. (2017)
  • Author(s): Satoshi Harada , Takashi SeShigeru Ehara a, Takahiro Sato , Koichiro Sera, Shyoko Goto.
  • Organizer: 59th Annual Meeting of America Society of Radiation Oncology, 2017
  • Int'l Joint Research
• [Presentation] Treatment of primary tumors through immunogenic cell death, with concurrent treatment of metastasized tumors through the abscopal effect, via targeted anti-CD4 siRNA, HMGB1, and ATP nanoparticles combined with radiotherapy (2017)
  • Author(s): Satoshi Harada , Takashi SeShigeru Ehara a, Takahiro Sato , Koichiro Sera, Shyoko Goto.
  • Organizer: 103rd Annual Meeting of Radiological Society of North America, 2017
  • Int'l Joint Research