Novel treatment of peritoneal dissemination by induction of anti-tumor immunity in the omentum using NKT cell activation vector

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18090
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kobe University
• Principal Investigator: Arimoto Akira 神戸大学, 医学研究科, 医学研究員 (20778766)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 大腸癌 / 腹膜播種 / milky spot / CD8+T細胞 / T細胞疲弊 / NKT細胞

Outline of Final Research Achievements

A mouse model of peritoneal dissemination was developed, which showed rapid progression and poor prognosis. Analysis of the tumor immune microenvironment showed that intraperitoneal cytokines markedly increased G-CSF and IL-6 and that PMN-MDSCs progressed with the disease.Qualitative evaluation of the NKT cell activation vaccine vector showed that it induced NKT cells and NK cells, and CD8+ T cells. We succeeded in showing that the vaccine was prophylactic against a subcutaneous tumor inoculation model, and we also succeeded in showing its efficacy in a lung metastasis model.
Currently, we are in the process of verifying the therapeutic results in a peritoneal seeding model.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害剤の癌治療への導入以降、免疫が癌治療に与えるインパクトが十分であったが、次なる治療として、その耐性に対する克服が重要となる。NKT細胞及びα-Galが人間との相同性があるため、NKT細胞活性化ワクチンベクターを開発し、腹膜播種といった難治性癌モデルに対して、その克服に関して前臨床モデルで示すことができることは、非常に期待のできる治療であると考える。消化器癌治療への恩恵をもたらす社会的にも、有意義であると考える。