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Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial.
- Source :
-
Nature [Nature] 2019 Jan; Vol. 565 (7738), pp. 234-239. Date of Electronic Publication: 2018 Dec 19. - Publication Year :
- 2019
-
Abstract
- Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses <superscript>1,2</superscript> and can function as bona fide antigens that facilitate tumour rejection <superscript>3</superscript> . Here we demonstrate that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma <superscript>4-6</superscript> , is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load <superscript>1,7</superscript> and an immunologically 'cold' tumour microenvironment <superscript>8</superscript> . 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 <superscript>+</superscript> and CD8 <superscript>+</superscript> 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.
- Subjects :
- Adult
Aged
DNA Methylation
DNA Modification Methylases genetics
DNA Repair Enzymes genetics
Dexamethasone administration & dosage
Glioblastoma diagnosis
Glioblastoma genetics
Humans
Middle Aged
Promoter Regions, Genetic genetics
Receptors, Antigen, T-Cell immunology
Tumor Suppressor Proteins genetics
Young Adult
Antigens, Neoplasm immunology
Cancer Vaccines immunology
Glioblastoma immunology
Glioblastoma therapy
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 565
- Issue :
- 7738
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 30568305
- Full Text :
- https://doi.org/10.1038/s41586-018-0792-9