An attempt to identify new antigens recognized by tumor-specific cytotoxic T lymphocytes using a HLA-modified ovarian cancer cell line as an artificial antigen presenting cell

2014 Fiscal Year Final Research Report

• Project/Area Number: 24659727
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Nagoya University
• Principal Investigator: KIKKAWA Fumitaka 名古屋大学, 医学(系)研究科(研究院), 教授 (40224985)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Shiro 名古屋大学, 医学部附属病院, 助教 (20612758) ; SHIBATA Kiyosumi 名古屋大学, 医学系研究科, 准教授 (90335026)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 卵巣癌 / 腫瘍免疫療法

Outline of Final Research Achievements

We built a novel method for inducing cancer-reactive cytotoxic T lymphocytes (CTLs) restricted to an HLA allele of interest. We used an artificial antigen presenting cell (aAPC), TOV21G that express a single HLA-A*24:02 allele and was originally derived from an ovarian clear cell carcinoma. Several CTL clones were established using aAPC stimulation. Then, cDNA library construction using mRNA extracted from the parental TOV21G cells and subsequent expression cloning was conducted.
These experiments revealed that a CTL clone recognized a minimal epitope peptide RYEFGQALF, which was derived from an autoantigen claudin-1 presented by HLA-A24:02 molecules.
Another clone responded not only to ovarian cancer cells in the context of HLA-A*24:02 but also to allogeneic HLA-Cw*07:02 molecules through cross-reactive TCR recognition. Expression screening using a cDNA library revealed that this alloreactivity was mediated through the 9-mer peptide VRTPYTMSY, derived from RNA-binding motif protein 4.

Free Research Field

婦人科腫瘍学