Development of polymeric micellar nanoparticle vaccines using immune checkpoint molecules

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22823
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Nihon University
• Principal Investigator: TSUKAMOTO Masako 日本大学, 医学部, 専修指導医 (80570910)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 免疫チェックポイント / T細胞

Outline of Final Research Achievements

We need to overcome the tumor microenvironment that includes the proteins produced by all of the cells present in the tumor that support the growth of the cancer cells. Modifying CD155 which is a common ligand for DNAM-1 (DNAX Accessory Molecule-1, CD226) and TIGIT (T-cell immunoreceptor with Ig and ITIM domains), we would create a vaccine that could control the balance between activity and suppression. Then, we investigated the relationship between TCR (T cell receptor), DNAM-1, and TIGIT. The presence of TIGIT suppressed TCR micro cluster.
DNAM-1 strongly bonded to CD155 compared with TIGIT, this results suggested CD155 modification would needed to argument TIGIT-CD155 reaction.

Free Research Field

免疫

Academic Significance and Societal Importance of the Research Achievements

進行した腫瘍では免疫細胞の疲弊化や制御性T細胞の増加など局所環境が免疫抑制状態に陥る『がん微小環境』による無効化が障害となっている。その打破として様々な抗がん剤やがんワクチンが臨床応用されており、免疫チェックポイント阻害薬もあげられる。TIGITは免疫チェックポイント分子の1つであり、次世代の免疫チェックポイント阻害薬として開発が進められている。T細胞の活性化の過程でTIGITが重要であることが示唆された。