Actively personalized vaccination trial for newly diagnosed glioblastoma
A phase I trial (GAPVAC‑101) demonstrated that personalized vaccines using both unmutated antigens and neoepitopes are feasible, safe and elicit strong CD8⁺ and CD4⁺ T‑cell immune responses in patients with newly diagnosed glioblastoma.
Patients with glioblastoma currently do not sufficiently benefit from recent breakthroughs in cancer treatment that use checkpoint inhibitors. For treatments using checkpoint inhibitors to be successful, a high mutational load and responses to neoepitopes are thought to be essential. There is limited intratumoural infiltration of immune cells in glioblastoma and these tumours contain only 30–50 non‑synonymous mutations. Exploitation of the full repertoire of tumour antigens—both unmutated antigens and neoepitopes—may offer more effective immunotherapies, especially for tumours with a low mutational load. Here, in the phase I trial GAPVAC‑101 of the Glioma Actively Personalized Vaccine Consortium (GAPVAC), we integrated highly individualized vaccinations with both types of tumour antigens into standard care to optimally exploit the limited target space for patients with newly diagnosed glioblastoma. Fifteen patients with glioblastomas positive for human leukocyte antigen (HLA)-A*02:01 or HLA-A*24:02 were treated with a vaccine (APVAC1) derived from a premanufactured library of unmutated antigens followed by treatment with APVAC2, which preferentially targeted neoepitopes. Personalization was based on mutations and analyses of the transcriptomes and immunopeptidomes of the individual tumours. The GAPVAC approach was feasible and vaccines that had poly‑ICLC and granulocyte‑macrophage colony‑stimulating factor as adjuvants displayed favourable safety and strong immunogenicity. Unmutated APVAC1 antigens elicited sustained responses of central memory CD8⁺ T cells. APVAC2 induced predominantly CD4⁺ T cell responses of T helper 1 type against predicted neoepitopes.
Evidence level: Állatkísérletes. Állatmodellben vizsgálták.