Exploiting the glioblastoma peptidome to discover novel tumour-associated antigens for immunotherapy

被引:151
作者
Dutoit, Valerie [2 ]
Herold-Mende, Christel [3 ]
Hilf, Norbert [4 ]
Schoor, Oliver [4 ]
Beckhove, Philipp [5 ]
Bucher, Judith [3 ]
Dorsch, Katharina [3 ]
Flohr, Sylvia [4 ]
Fritsche, Jens [4 ]
Lewandrowski, Peter [4 ]
Lohr, Jennifer [3 ]
Rammensee, Hans-Georg [6 ]
Stevanovic, Stefan [6 ]
Trautwein, Claudia [4 ]
Vass, Verona [4 ]
Walter, Steffen [4 ]
Walker, Paul R. [2 ]
Weinschenk, Toni [4 ]
Singh-Jasuja, Harpreet [4 ]
Dietrich, Pierre-Yves [1 ,2 ]
机构
[1] Univ Hosp Geneva, Ctr Oncol, Lab Tumour Immunol, CH-1211 Geneva 14, Switzerland
[2] Univ Geneva, Ctr Oncol, Lab Tumour Immunol, CH-1211 Geneva 14, Switzerland
[3] Heidelberg Univ, Dept Neurosurg, Div Neurosurg Res, D-69120 Heidelberg, Germany
[4] Immat Biotechnol GmbH, D-72076 Tubingen, Germany
[5] German Canc Res Ctr, Translat Immunol Unit, D-69120 Heidelberg, Germany
[6] Univ Tubingen, Dept Immunol, Inst Cell Biol, D-72076 Tubingen, Germany
关键词
glioblastoma; immunotherapy; peptidome; tumour antigen; tumour-infiltrating lymphocytes; CHONDROITIN SULFATE PROTEOGLYCAN; TENASCIN-C; T-CELLS; GLIOMA-CELL; PROGRESSION; EXPRESSION; AVIDITY; SELECTION; GROWTH; IDENTIFICATION;
D O I
10.1093/brain/aws042
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Peptides presented at the cell surface reflect the protein content of the cell; those on HLA class I molecules comprise the critical peptidome elements interacting with CD8 T lymphocytes. We hypothesize that peptidomes from ex vivo tumour samples encompass immunogenic tumour antigens. Here, we uncover >6000 HLA-bound peptides from HLA-A*02(+) glioblastoma, of which over 3000 were restricted by HLA-A*02. We prioritized in-depth investigation of 10 glioblastoma-associated antigens based on high expression in tumours, very low or absent expression in healthy tissues, implication in gliomagenesis and immunogenicity. Patients with glioblastoma showed no T cell tolerance to these peptides. Moreover, we demonstrated specific lysis of tumour cells by patients' CD8(+) T cells in vitro. In vivo, glioblastoma-specific CD8(+) T cells were present at the tumour site. Overall, our data show the physiological relevance of the peptidome approach and provide a critical advance for designing a rational glioblastoma immunotherapy. The peptides identified in our study are currently being tested as a multipeptide vaccine (IMA950) in patients with glioblastoma.
引用
收藏
页码:1042 / 1054
页数:13
相关论文
共 47 条
[41]   Identification of HLA-A2-restricted CTL epitopes of a novel tumour-associated antigen, KIF20A, overexpressed in pancreatic cancer [J].
Imai, K. ;
Hirata, S. ;
Irie, A. ;
Senju, S. ;
Ikuta, Y. ;
Yokomine, K. ;
Harao, M. ;
Inoue, M. ;
Tomita, Y. ;
Tsunoda, T. ;
Nakagawa, H. ;
Nakamura, Y. ;
Baba, H. ;
Nishimura, Y. .
BRITISH JOURNAL OF CANCER, 2011, 104 (02) :300-307
[42]   Galectin 9 and PINCH, novel immunotherapy targets of renal cell carcinoma: a rationale to find potential tumour antigens and the resulting cytotoxic T lymphocytes induced by the derived peptides [J].
Kawashima, Hidenori ;
Obayashi, Aiko ;
Kawamura, Marie ;
Masaki, Sakae ;
Tamada, Satoshi ;
Iguchi, Taro ;
Uchida, Junji ;
Kuratsukuri, Katsuyuki ;
Tanaka, Tomoaki ;
Nakatani, Tatsuya .
BJU INTERNATIONAL, 2014, 113 (02) :320-332
[43]   Sialic acid-targeted cyclodextrin-based nanoparticles deliver CSF-1R siRNA and reprogram tumour-associated macrophages for immunotherapy of prostate cancer [J].
Sun, Yao ;
Cronin, Michael F. ;
Mendonca, Monique C. P. ;
Guo, Jianfeng ;
O'Driscoll, Caitriona M. .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2023, 185
[44]   A non-aggregated and tumour-associated macrophage-targeted photosensitiser for photodynamic therapy: a novel zinc(II) phthalocyanine containing octa-sulphonates [J].
Li, Xing-Shu ;
Ke, Mei-Rong ;
Zhang, Miao-Fen ;
Tang, Qing-Qing ;
Zheng, Bi-Yuan ;
Huang, Jian-Dong .
CHEMICAL COMMUNICATIONS, 2015, 51 (22) :4704-4707
[45]   Expression of nine tumour antigens in a series of human glioblastoma multiforme:: interest of EGFRvIII, IL-13Rα2, gp100 and TRP-2 for immunotherapy [J].
Saikali, Stephan ;
Avril, Tony ;
Collet, Brigitte ;
Hamlat, Abderrahmane ;
Bansard, Jean-Yves ;
Drenou, Bernard ;
Guegan, Yvon ;
Quillien, Veronique .
JOURNAL OF NEURO-ONCOLOGY, 2007, 81 (02) :139-148
[46]   Expression of nine tumour antigens in a series of human glioblastoma multiforme: interest of EGFRvIII, IL-13Rα2, gp100 and TRP-2 for immunotherapy [J].
Stéphan Saikali ;
Tony Avril ;
Brigitte Collet ;
Abderrahmane Hamlat ;
Jean-Yves Bansard ;
Bernard Drenou ;
Yvon Guegan ;
Véronique Quillien .
Journal of Neuro-Oncology, 2007, 81 :139-148
[47]   Enhancement of antitumour immunity by a novel chemotactic antigen DNA vaccine encoding chemokines and multiepitopes of prostate-tumour-associated antigens [J].
Qin, HJ ;
Zhou, CX ;
Wang, DM ;
Ma, WB ;
Liang, X ;
Lin, C ;
Zhang, YH ;
Zhang, SR .
IMMUNOLOGY, 2006, 117 (03) :419-430