Novel H3.3K27M-derived Neoantigen and TCR

A majority of diffuse midline gliomas in children and young adults harbor the amino acid substitution from lysine (K) to methionine (M) at position 27 (K27M mutation) in the histone 3 variant H3.3. My lab recently found that a peptide encompassing the K27M mutation induces specific cytotoxic T lymphocytes (CTL) responses in human leukocyte antigen (HLA)-A2+ CD8+ T-cells. Furthermore, we have cloned cDNA for T-cell receptor (TCR) α- and β-chains derived from an H3.3.K27M-specific CTL clone. We showed human T-cells transduced with the TCR specifically respond to the H3.3.K27M epitope and kill HLA-A2+ H3.3.K27M+ glioma both in vitro and in vivo. We are currently developing a novel immunotherapy using T cells transduced with the K27M-specific TCR. 

Related Publication

Chheda ZS, Kohanbash G, Okada K, Jahan N, Sidney J, Pecoraro M, Yang X, Carrera DA, Downey KM, Shrivastav S, Liu S, Lin Y, Lagisetti C, Chuntova P, Watchmaker PB, Mueller S, Pollack IF, Rajalingam R, Carcaboso AM, Mann M, Sette A, Garcia, KC, Hou Y and Okada H: Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T-cell therapy. J. Exp. Med. 215 (1) 141-157 (2018) PMC5748856

Who works on this project in the Okada Lab?