Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial
Author(s)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; Gabriel, Stacey; Getz, Gad Asher; Lander, Eric Steven; 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.; ... Show more Show less
MetadataShow full item record
Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses1,2 and can function as bona fide antigens that facilitate tumour rejection3. Here we demonstrate that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma4–6, is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load1,7 and an immunologically ‘cold’ tumour microenvironment8. 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.
DepartmentBroad Institute of MIT and Harvard; Massachusetts Institute of Technology. Department of Biology
Springer Science and Business Media LLC
Keskin, Derin B. et al. "Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial." Nature 565, 7738 (December 2018): 234–239 © 2018 Springer Nature Limited
Author's final manuscript