Basic research on personalized iPSDCs cancer vaccine therapy targeting neoantigen

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18131
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Wakayama Medical University
• Principal Investigator: Kitadani Junya 和歌山県立医科大学, 医学部, 助教 (30596979)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: iPS細胞 / iPSDC / 樹状細胞療法 / 癌免疫療法 / ネオアンチゲン

Outline of Final Research Achievements

iPS cells were established from peripheral blood mononuclear cells of 3 patients with colorectal cancer who agreed to participate in the study. The ivtRNA amplified from the mRNA extracted from the tumor was introduced into the iPSDCs. It was demonstrated in all patients that the CTLs obtained by stimulation with iPSDCs-ivtRNA showed cancer-specific cytotoxicity to the patient's own cancer cells established by the CTOS method. Furthermore, this vaccine system was demonstrated to induce a neoantigen-mediated immune response by ELISPOT assay with candidate neoantigen peptide.

Free Research Field

癌免疫治療

Academic Significance and Societal Importance of the Research Achievements

我々は、担癌患者における成熟能や抗原提示能の低下といった樹状細胞療法の弱点を克服するために、iPS細胞由来樹状細胞 (iPSDCs) を用いた癌ワクチン療法の基礎研究を行ってきた。本研究の目的は、正常細胞には発現せず、腫瘍における遺伝子変異によってのみ発現するneoantigenを標的とした、副作用が少なく、且つ強力な抗原提示が可能な個別化癌ワクチン療法の基礎的研究を行うことであった。本研究の結果からivtRNAワクチンは、neoantigenを介した強力な腫瘍特異的細胞傷害活性を示すことが証明でき、これは、難治癌克服への第一歩となると考える。