Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients
Open accessAbstract
Background: Peptide vaccines offer the opportunity to elicit glioma-specific T cells with tumor killing ability. Using antigens eluted from the surface of glioblastoma samples, we designed a phase I/II study to test safety and immunogenicity of the IMA950 multipeptide vaccine adjuvanted with poly-ICLC (polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose) in human leukocyte antigen A2+ glioma patients. Methods: Adult patients with newly diagnosed glioblastoma (n = 16) and grade III astrocytoma (n = 3) were treated with radiochemotherapy followed by IMA950/poly-ICLC vaccination. The first 6 patients received IMA950 (9 major histocompatibility complex [MHC] class I and 2 MHC class II peptides) intradermally and poly-ICLC intramuscularly (i.m.). After protocol amendment, IMA950 and poly-ICLC were mixed and injected subcutaneously (n = 7) or i.m. (n = 6). Primary endpoints were safety and immunogenicity. Secondary endpoints were overall survival, progression-free survival at 6 and 9 months, and vaccine-specific peripheral cluster of differentiation (CD)4 and CD8 T-cell responses. Results: The IMA950/poly-ICLC vaccine was safe and well tolerated. Four patients presented cerebral edema with rapid recovery. For the first 6 patients, vaccine-induced CD8 T-cell responses were restricted to a single peptide and CD4 responses were absent. After optimization of vaccine formulation, we observed multipeptide CD8 and sustained T helper 1 CD4 T-cell responses. For the entire cohort, CD8 T-cell responses to a single or multiple peptides were observed in 63.2% and 36.8% of patients, respectively. Median overall survival was 19 months for glioblastoma patients. Conclusion: We provide, in a clinical trial, using cell surface-presented antigens, insights into optimization of vaccines generating effector T cells for glioma patients. Trial registration: Clinicaltrials.gov NCT01920191.
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The epitopes encoded by CVGBM have previously induced T-cell responses in patients with GBM when given as peptide-based immunotherapeutics in the GAPVAC-101 or IMA950 studies.
“The epitopes encoded by CVGBM have previously induced T-cell responses in the GAPVAC-101 or IMA950 studies in patients with GBM when given as peptide-based immunotherapeutics in combination with adjuvants [14, 15].”
From Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma (2025) · cites this paper as [15]
The Introduction identifies IMA950 as a peptide vaccine, and Safety Data reports tumor-peptide-specific CD8 T-cell responses in 62.5% of the GBM-only cohort. The paper does not identify CVGBM or establish that the epitopes it encodes are the IMA950 epitopes, so it supports the IMA950 response finding but not that overlap. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe eight CVGBM-encoded epitopes have induced immune responses in previous clinical trials as peptide-based immunotherapeutics.
“CVGBM encodes eight epitopes that are frequently presented on the surface of GBM tumour samples and have induced immune responses in previous clinical trials as peptide-based immunotherapeutics [14, 15].”
From Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma (2025) · cites this paper as [15]
The Introduction (page unavailable) describes IMA950 as containing nine CD8 T-cell epitopes derived from eight proteins, not eight epitopes. The Safety Data and Discussion (pages unavailable) report vaccine-induced responses to tumor peptides, but do not establish that all eight epitopes described in the claim induced responses. (LLM, conf=0.87)
Experimental — accuracy not yet measuredCVGBM encodes eight epitopes that are frequently presented on the surface of GBM tumour samples.
“CVGBM encodes eight epitopes that are frequently presented on the surface of GBM tumour samples and have induced immune responses in previous clinical trials as peptide-based immunotherapeutics [14, 15].”
From Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma (2025) · cites this paper as [15]
The Introduction (page unavailable) says that peptides formulated in IMA950 were eluted from GBM tumour surfaces and presented on GBM samples in vivo. But it describes nine CD8 T-cell epitopes from eight proteins, not eight epitopes, and does not identify CVGBM or establish which epitopes it encodes. (LLM, conf=0.86)
Experimental — accuracy not yet measuredBoth the GAPVAC-101 and IMA950 immunotherapeutics were well tolerated and induced epitope-specific CD8+ T-cell responses.
“Both immunotherapeutics, which shared some peptides, were well tolerated and induced epitope-specific CD8+ T-cell responses [14, 15].”
From Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma (2025) · cites this paper as [15]
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References 30 · Cited by 147
- Authors
- Migliorini, D., Dutoit, V., Allard, M., Grandjean Hallez, N., Marinari, E., Widmer, V., Philippin, G., Corlazzoli, F., Gustave, R., Kreutzfeldt, M., Blazek, N., Wasem, J., Hottinger, A., Koka, A., Momjian, S., Lobrinus, A., Merkler, D., Vargas, M.-I., Walker, P. R., Patrikidou, A., & Dietrich, P.-Y.
- Affiliations
- University Hospital of Geneva (CH)
- University of Geneva (CH)
- Department of Oncology, Clinical Research Unit, Dr Dubois Ferrière Dinu Lipatti Research Foundation, Geneva University Hospital, Geneva, Switzerland
- Corresponding author
- Hottinger, Andreas
- Dietrich, Pierre-Yves
- ORCID
- Venue
- Neuro-Oncology
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-05-03
- Volume
- 21
- Issue
- 7
- Pages
- 923-933
- ISSN
- 1522-8517 (ISSN-L)
- 1523-5866
- PMC
- PMC6620642
- OpenAlex
- W2914631114
- Cited by
- 147
- References
- 30
- Citations by year
- 2026: 13 · 2025: 24 · 2024: 21 · 2023: 25 · 2022: 23 · 2021: 22 · 2020: 13 · 2019: 6
- FWCI
- 8.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Neuro-Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (acceptedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- NIH
- Gateway for Cancer Research (G-12-GOO)
- Rising Tide Foundation
- Fondation Lionel Perrier
- Association Frederic Fellay
- Fondation Privée des Hôpitaux Universitaires de Genève; Fond’action; and Association Marietta
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- poly-ICLC, glioblastoma, malignant astrocytoma, peptide vaccine, vaccine adjuvants, HLA-A2, CD8+ T cell responses, CD4+ T cell responses, tumor-specific T cells, cell surface antigens, vaccine safety, immunogenicity, chemoradiotherapy, overall survival
- MeSH terms
- Adult, Aged, Astrocytoma, Carboxymethylcellulose Sodium, Combined Modality Therapy, Female, Follow-Up Studies, Glioblastoma, Humans, Male, Middle Aged, Peptides, Poly I-C, Polylysine, Prognosis, Survival Rate, CD8-Positive T-Lymphocytes, Cancer Vaccines, Vaccines, Subunit, Young Adult, Chemoradiotherapy
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