Development of HTLV-I-specific anti-cancer therapy by using single chain T cell receptors and single chain trimers of MHC-I.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590547
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Hokkaido University
• Principal Investigator: OHASHI Takashi 北海道大学, 遺伝子病制御研究所, 准教授 (10282774)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: HTLV-I / 成人T細胞白血病 / 動物モデル / 免疫治療 / ウイルス療法

Outline of Final Research Achievements

The potential for novel therapies against Human T-cell leukemia virus type I (HTLV-I) induced-adult T-cell leukemia (ATL) has been assessed in an originally developed rat model of HTLV-I infection. The results indicate that combined treatment with m8Δ/RT1AlSCTax180L, which can express a single chain trimer of rat MHC-I with a Tax-epitope, and the epitope-specific CTL line, 4O1/C8, increased the cytolysis of FPM1V.EFGFP/8R cells, a CTL-resistant subclone of HTLV-I-infected FPM1 cells, compared with that using 4O1/C8 and m8Δ presenting an unrelated peptide, suggesting that the activation of 4O1/C8 by m8Δ/RT1AlSCTax180L further enhanced the killing of the HTLV-I-infected cells. Our results indicate that combined therapy of oncolytic m8Δ/RT1AlSCTax180L, and HTLV-I-specific CTLs may be effective for eradication of HTLV-I-infected cells, which evade from CTL lysis and potentially develop ATL. The present results should be useful for further verifying the strategies to fight against ATL.

Free Research Field

ウイルス学