Development of CAR that can recognize pMHC molecule derived from endogenous antigen of tumor cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K14631
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Mie University
• Principal Investigator: Akahori Yasushi 三重大学, 医学系研究科, 特任講師(研究担当) (80221711)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: CAR / TCR-like antibody / pMHC complex / antibody library / screen

Outline of Final Research Achievements

In this study, I selected WT1 as my target. Next, I isolated TCR-like antibody clones by combining magnet beads screening, peptide pulsed T2A24 cell screening and plate screening strategy and isolated twelve type of antibodies. After testing recognition specificity and affinity, I chose #213 as candidate clone for chimeric antigen receptor (CAR) therapy.
Next, I investigated whether it is safe for cancer therapy. In the first, I checked critical amino acids for #213 CAR recognition by alanine substitution. Among nine amino acids of WT1p235-243, 2M, 3T, 4W, 5N were shown to be critical for #213 CAR recognition. Next, I further tested amino acid substitution by similar ones. 2W, 3N, 3S, 4F and 5H were shown to be recognized by #213 CAR. After blast search, I chose 42 off-target candidate peptides. In them, two peptides, that were expressed in normal tissues, were shown to be recognized by #213 CAR.

Free Research Field

免疫学及び分子生物学