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2023 Fiscal Year Final Research Report

Development of a novel therapy for lung cancer using Non-viral chimeric antigen receptor (CAR) T cells

Research Project

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Project/Area Number 21K15547
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionShinshu University

Principal Investigator

Miura Kentaro  信州大学, 医学部附属病院, 助教(特定雇用) (70624716)

Project Period (FY) 2021-04-01 – 2024-03-31
Keywords肺癌 / CAR-T細胞 / ピギーバックトランスポゾン / IGF1受容体
Outline of Final Research Achievements

In this study, we developed Ligand-type CAR-T cells targeting the IGF1 receptor, which has been reported to be overexpressed in lung cancer, using a non-viral transduction method. In the early stage of development, when IGF1 was employed as the antigen recognition site, the CAR expression rate decreased over time. We focused on the maturation process of IGF1 and used a mutant of immature IGF1, which showed stable CAR expression and high antitumor efficacy against IGF1R-expressing lung adenocarcinoma. In addition, with the aim of achieving a sustained effect in vivo, amino acid mutations were added to minimize the effect of proteins that inhibit the reaction between IGF1 and IGF1R.

Free Research Field

肺癌

Academic Significance and Societal Importance of the Research Achievements

本研究の特徴は、CAR-T細胞の抗原認識部位にヒトLigandを採用していること、またCAR遺伝子の導入に非ウイルス導入法であるpiggyBac法を用いていることである。ヒトLigandは、従来の抗体の可変領域を用いるscFvと異なり、この抗原認識部位自体に対する抗体産生を原因とする効果減弱などの懸念がなく、標的となる受容体との適切な結合力によって持続的な効果が期待出来る。また、本開発で採用したpiggyBac法は、ウイルス導入法よりも安価かつ安全性が高いとされていることから、本開発品は臨床応用が期待出来ると考える。

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Published: 2025-01-30  

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