Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial

By D. Keskin, Annabelle J Anandappa, Jing Sun, I. Tirosh, N. Mathewson, Shuqiang Li, G. Oliveira, A. Giobbie-Hurder, K. Felt, E. Gjini and 41 more. Nature, 2018

1,215 citations recorded by the source corpus.

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. Neoantigen-targeting vaccines are a feasible therapy for tumours with a low mutation burden and immunologically ‘cold’ tumour microenvironment, as neoantigen-specific T cells from the peripheral blood migrate into intracranial glioblastoma, thereby altering the immune milieu of the glioblastoma.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/58c93102019e475c3d3af1f026f1a6a0fefa1ab7

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

  1. Sandra Hervás-Stubbs
  2. I. Melero

In Oncology

  1. I. Melero

Citations in the corpus