Identification of factors that determine the fate of functional T cells in vivo and development of effective TCR gene-modified T cell therapy

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390300
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Mie University
• Principal Investigator: IKEDA Hiroaki 三重大学, 医学(系)研究科(研究院), 教授 (40374673)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: T細胞 / マルチファンクション性 / T細胞輸注療法 / 遺伝子治療 / 癌 / 免疫記憶 / T細胞受容体 / キメラ抗原受容体

Outline of Final Research Achievements

We found that CD28 stimuli induced short-lived but highly cytotoxic T cells whereas VLA-4/5 stimuli induced T cells with memory formation potential and high multifuctionality upon recall. We performed a phase I clinical trial with T cells with genetically engineered to express MAGE-A4-specific TCR for esophageal cancer patients. In this trial, we found that the long-term existence of the infused cells did not correlate with the clinical response when the patients did not receive lympho-depletive pre-treatment. Utilizing an original retroviral vector that inhibits the expression of endogenous TCR, we demonstrated a model of adoptive therapy with allogeneic T cells that induce less GvHD and increased tumor reactivity. We generated an antibody that reacted to the complex of HLA and a peptide from intracellular antigen and showed the usefulness of a chimeric antigen receptor that utilize this antibody.

Free Research Field

腫瘍免疫、細胞療法、遺伝子治療