6UJ7

Crystal structure of HLA-B*07:02 with R140Q mutant IDH2 peptide

6UJ7 の概要

• エントリーDOI: 10.2210/pdb6uj7/pdb
• 分子名称: HLA class I histocompatibility antigen, B-7 alpha chain, Beta-2-microglobulin, Isocitrate dehydrogenase [NADP], mitochondrial, ... (7 entities in total)
• 機能のキーワード: hla-b7, mhc-i, immunotherapy, idh2, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 98999.63

構造登録者

Miller, M.S.,Thirawatananond, P.,Gabelli, S.B. (登録日: 2019-10-02, 公開日: 2021-05-05, 最終更新日: 2024-10-23)

主引用文献

Hwang, M.S.,Miller, M.S.,Thirawatananond, P.,Douglass, J.,Wright, K.M.,Hsiue, E.H.,Mog, B.J.,Aytenfisu, T.Y.,Murphy, M.B.,Aitana Azurmendi, P.,Skora, A.D.,Pearlman, A.H.,Paul, S.,DiNapoli, S.R.,Konig, M.F.,Bettegowda, C.,Pardoll, D.M.,Papadopoulos, N.,Kinzler, K.W.,Vogelstein, B.,Zhou, S.,Gabelli, S.B.
Structural engineering of chimeric antigen receptors targeting HLA-restricted neoantigens.
Nat Commun, 12:5271-5271, 2021

PubMed Abstract: Chimeric antigen receptor (CAR) T cells have emerged as a promising class of therapeutic agents, generating remarkable responses in the clinic for a subset of human cancers. One major challenge precluding the wider implementation of CAR therapy is the paucity of tumor-specific antigens. Here, we describe the development of a CAR targeting the tumor-specific isocitrate dehydrogenase 2 (IDH2) with R140Q mutation presented on the cell surface in complex with a common human leukocyte antigen allele, HLA-B*07:02. Engineering of the hinge domain of the CAR, as well as crystal structure-guided optimization of the IDH2-HLA-B*07:02-targeting moiety, enhances the sensitivity and specificity of CARs to enable targeting of this HLA-restricted neoantigen. This approach thus holds promise for the development and optimization of immunotherapies specific to other cancer driver mutations that are difficult to target by conventional means.

PubMed: 34489470
DOI: 10.1038/s41467-021-25605-4

実験手法

X-RAY DIFFRACTION (1.9 Å)