Development of novel immunotherapy against driver-oncogene-positve lung cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16126
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Hyogo Medical University
• Principal Investigator: Horio Daisuke 兵庫医科大学, 医学部, 助教 (40815635)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ドライバー遺伝子変異・転座陽性肺癌 / 小分子阻害薬 / 免疫チェックポイント分子 / Drug tolerant persisters

Outline of Final Research Achievements

Small molecule inhibitors against driver-oncogene positive-lung cancer are expected to exert dramatic antitumor effect. However, a few cells called drug-tolerant persisters (DTPs) are intrinsically resistant to them and develop recurrence. In contrast to the difficulty of elimination of these DTPs, they are numerically small. Therefore, once effective antitumor immunity can be induced to them, radical cure of the driver-oncogene positive-lung cancer would be possible.
We found that specific tyrosine kinase inhibitor strongly induced the expression of Galectin-9, one of immune checkpoint molecules, in lung cancer cells. Although adaptive immunity is said to be less effective due to the lack of neoantigens in driver-oncogene positive-lung cancer, activation of innate immunity by regulating Galectin-9 is a promising way to cure by eliminating DTPs .

Free Research Field

難治性胸部悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

現在actionable driver oncogeneとして肺癌においては、9種類が報告されている。本研究では特に頻度の高いEGFR遺伝子変異陽性非小細胞肺癌とALK融合遺伝子陽性非小細胞肺癌を念頭に実験を行ったが、これらの症例は肺癌の60%を占める肺腺癌の半数以上を占め、肺癌全体の治療成績の向上のためにはこれらの症例の予後のさらなる改善は不可欠である。
特異的小分子阻害薬は極めて有効だが、根治する事は不可能で、一旦薬剤が奏功していても転移再発は不可避である。本研究で自然免疫系を利用した抗腫瘍免疫を誘導できれば、小分子阻害薬の持続的な効果延長が期待でき、予後の改善に繋がると期待される。