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Keskin, Derin B; Anandappa, Annabelle J; Sun, Jing; Tirosh, Itay; Mathewson, Nathan D; Li, Shuqiang; Oliveira, Giacomo; Giobbie-Hurder, Anita; Felt, Kristen; Gjini, Evisa; Shukla, Sachet A; Hu, Zhuting; Li, Letitia; Le, Phuong M; Allesøe, Rosa L; Richman, Alyssa R; Kowalczyk, Monika S; Abdelrahman, Sara; Geduldig, Jack E; Charbonneau, Sarah; Pelton, Kristine; Iorgulescu, J Bryan; Elagina, Liudmila; Zhang, Wandi; Olive, Oriol; McCluskey, Christine; Olsen, Lars R; Stevens, Jonathan; Lane, William J; Salazar, Andres M; Daley, Heather; Wen, Patrick Y; Chiocca, E Antonio; Harden, Maegan; Lennon, Niall J; Gabriel, Stacey; Getz, Gad; Lander, Eric S; Regev, Aviv; Ritz, Jerome; Neuberg, Donna; Rodig, Scott J; Ligon, Keith L; Suvà, Mario L; Wucherpfennig, Kai W; Hacohen, Nir; Fritsch, Edward F; Livak, Kenneth J; Ott, Patrick A; Wu, Catherine J; Reardon, David A
Nature (London), 01/2019, Letnik: 565, Številka: 7738Journal Article
Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses and can function as bona fide antigens that facilitate tumour rejection . Here we demonstrate that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma , is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load and an immunologically 'cold' tumour microenvironment . We used personalized neoantigen-targeting vaccines to immunize patients newly diagnosed with glioblastoma following surgical resection and conventional radiotherapy in a phase I/Ib study. Patients who did not receive dexamethasone-a highly potent corticosteroid that is frequently prescribed to treat cerebral oedema in patients with glioblastoma-generated circulating polyfunctional neoantigen-specific CD4 and CD8 T cell responses that were enriched in a memory phenotype and showed an increase in the number of tumour-infiltrating T cells. Using single-cell T cell receptor analysis, we provide evidence that neoantigen-specific T cells from the peripheral blood can migrate into an intracranial glioblastoma tumour. Neoantigen-targeting vaccines thus have the potential to favourably alter the immune milieu of glioblastoma.
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in: SICRIS
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