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Updated: Jan 31, 2026
The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma
Published on: April 16, 2019
Actively personalized vaccination trial for newly diagnosed glioblastoma
Norbert Hilf1, Sabrina Kuttruff-Coqui1, Katrin Frenzel2
1Immatics Biotechnologies GmbH, Tübingen, Germany.
Abstract:
Patients with glioblastoma currently do not sufficiently benefit from recent breakthroughs in cancer treatment that use checkpoint inhibitors1,2. For treatments using checkpoint inhibitors to be successful, a high mutational load and responses to neoepitopes are thought to be essential3. There is limited intratumoural infiltration of immune cells4 in glioblastoma and these tumours contain only 30-50 non-synonymous mutations5. Exploitation of the full repertoire of tumour antigens-that is, 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 (polyriboinosinic-polyribocytidylic acid-poly-L-lysine carboxymethylcellulose) 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.
Insights
Glioblastoma immunotherapy shows promise with personalized vaccines targeting both unmutated and neoantigens. This approach, integrating unmutated APVAC1 and neoepitope-targeting APVAC2 vaccines, demonstrated safety and strong immunogenicity in a Phase I trial.
Area of Science:
- Immunology
- Oncology
- Vaccine Development
Background:
- Glioblastoma (GBM) exhibits limited benefit from current checkpoint inhibitor immunotherapies due to low tumor mutational burden and immune cell infiltration.
- Effective immunotherapies for GBM may require targeting a broader range of tumor antigens, including both unmutated antigens and neoepitopes.
- Exploiting the full tumor antigen repertoire is crucial for enhancing treatment efficacy, particularly in low mutational load cancers.
Purpose of the Study:
- To evaluate the feasibility, safety, and immunogenicity of a personalized vaccine strategy for newly diagnosed glioblastoma.
- To integrate individualized vaccinations targeting both unmutated antigens and neoepitopes into standard care for glioblastoma patients.
- To assess the immune responses elicited by personalized vaccines in patients with human leukocyte antigen (HLA)-A*02:01 or HLA-A*24:02 positive glioblastomas.
Main Methods:
- A Phase I clinical trial (GAPVAC-101) involving fifteen newly diagnosed glioblastoma patients.
- Treatment involved a personalized vaccine (APVAC1) from a library of unmutated antigens, followed by a neoepitope-targeting vaccine (APVAC2).
- Vaccine personalization was guided by individual tumor mutation and transcriptome/immunopeptidome analyses.
Main Results:
- The Glioma Actively Personalized Vaccine Consortium (GAPVAC) approach was feasible and demonstrated favorable safety.
- Vaccines, with poly-ICLC and granulocyte-macrophage colony-stimulating factor adjuvants, showed strong immunogenicity.
- APVAC1 induced sustained CD8+ T cell responses against unmutated antigens, while APVAC2 elicited CD4+ T helper 1 cell responses against neoepitopes.
Conclusions:
- Personalized vaccination strategies combining unmutated and neoepitope antigens are feasible and immunogenic in glioblastoma.
- This approach holds potential for enhancing immunotherapy efficacy in glioblastoma by broadening the targeted antigen repertoire.
- The GAPVAC strategy warrants further investigation for its therapeutic benefit in glioblastoma patients.
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