Person: Iorgulescu, Julian
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Iorgulescu
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Julian
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Iorgulescu, Julian
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Publication Intratumoral T cell response detected after personal neoantigen vaccine in a phase Ib glioblastoma trial(Springer Nature) Keskin, Derin B.; Anandappa, Annabelle J.; Sun, Jing; Tirosh, Itay; Mathewson, Nathan; 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, Julian; Elagina, Liudmila; Zhang, Wandi; Olive, Oriol; McCluskey, Christine; Olsen, Lars R.; Stevens, Jonathan; Lane, William; 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; Hacohen, Nir; Fritsch, Edward F.; Livak, Kenneth J.; Ott, Patrick A.; Wu, Catherine; Reardon, David A.; Keskin, Derin; Sulva, MarioNeoantigens, derived from tumor-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses, and can function as bona fide tumor rejection antigens. Here, we demonstrate that a strategy of multi-epitope, personalized neoantigen vaccination, previously tested only in patients with high-risk melanoma, is feasible for tumors such as glioblastoma, which typically have a relatively low mutation load and an immunologically “cold” tumor microenvironment. We immunized patients with newly diagnosed GBM using personalized neoantigen-targeting vaccines following surgical resection and conventional radiotherapy in a phase I/Ib study. Patients who did not receive dexamethasone, a highly potent corticosteroid frequently prescribed to glioblastoma patients for cerebral edema, generated circulating polyfunctional neoantigen-specific CD4+ and CD8+ T-cell responses that were enriched for a memory phenotype, and increased tumor-infiltrating T-cells. Utilizing single-cell T-cell receptor analysis, we provide evidence that neoantigen-specific T-cells from the peripheral blood can migrate into an intracranial glioblastoma tumor. Neoantigen-targeting vaccines thus have the potential to favorably alter the immune milieu of glioblastoma.Publication Efficacy and Safety of Immune Checkpoint Blockade for Brain Metastases(Future Medicine Ltd, 2019-03-11) Harary, Maya; Reardon, David; Iorgulescu, Julian