gene delivery into lymphocytes using lymphatic administration and ultrasound

• Project/Area Number: 17K13039
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical systems
• Research Institution: Kindai University
• Principal Investigator: KATO Shigeki 近畿大学, 医学部, 助教 (90790767)
• Research Collaborator: KODAMA tetsuya
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ドラッグデリバリー / 超音波 / 腫瘍免疫 / リンパ節転移 / 免疫学 / リンパ / ウイルス / 癌

Outline of Final Research Achievements

Our study used MXH10/Mo-lpr/lpr mice, which develop systemic swelling of lymph nodes up to 10mm in diameter. Murine breast cancer cells were inoculated into the subiliac lymph node of these mice to deliver them to the downstream proper axillary lymph node, thereby developing a model of a metastatic lesion. In order to deliver doxorubicin (Dox) to the tumor lesions in the proper axillary lymph node via the lymphatic vessels, solutions containing Dox and nano/microbubbles were injected into the subiliac lymph node. After successful detection of nano/microbubbles in the proper axillary lymph node, the bubbles were destroyed by the application of destruction ultrasound; this resulted in the penetration of Dox into tumor tissues in the marginal sinuses and enhancement of its antitumor effects. This study is unique in that the treatment technique described was able to suppress the intranodal invasion of tumor cells and thereby preserve the lymphatic structure in the tumor-bearing lymph node.

Academic Significance and Societal Importance of the Research Achievements

がん死の原因はその 9 割以上が転移によるものである．リンパ管とその経路上に位置するリンパ節はがんの主な転移経路であり，効果的なリンパ節転移治療ががん治療成績の向上に直結する．従来の転移リンパ節治療法は，侵襲性，組織特異性，安全性，費用対効果の面で課題があった．本研究で提唱したリンパ管を介した薬剤投与と超音波による分子導入法は比較的安全で簡便な実験系で遂行可能であることから，従来のリンパ節転移治療法での課題を克服しうる可能性がある．さらに，本研究手法はリンパ球への遺伝子導入へとつながる可能性を示唆するものであり，免疫細胞への安全で効率的な遺伝子導入は新たながん免疫療法への展開が期待される．

Research Products

• [Journal Article] B7-H3 negatively modulates CTL-mediated cancer immunity (2018)
  • Author(s): Yonesaka K, Haratani K, Takamura S, Sakai H, Kato R, Takegawa N, Takahama T, Tanaka K, Hayashi H, Takeda M, Kato S, Maenishi O, Sakai K, Chiba Y, Okabe T, Kudo K, Hasegawa Y, Kaneda H, Yamato M, Hirotani K, Miyazawa M, Nishio K, Nakagawa K.
  • Journal Title: Clin Cancer Res. Volume: - Issue: 11 Pages: 2653-2664
  • DOI: 10.1158/1078-0432.ccr-17-2852
  • Peer Reviewed