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Neuro Oncol. 2019 Feb 12. doi: 10.1093/neuonc/noz040. [Epub ahead of print]

Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients.

Author information

1
Department of Oncology, Clinical Research Unit, Dr Dubois Ferrière Dinu Lipatti Research Foundation, Geneva University Hospital, Geneva, Switzerland.
2
Laboratory of Tumor immunology and Department of Oncology, Geneva University Hospital, Geneva, Switzerland.
3
Translational research center for oncohaematology, Department of Internal Medicine Specialties, University of Geneva, Geneva, Switzerland.
4
Neuropathology Division, Department of Pathology, Geneva University Hospital, Geneva, Switzerland.
5
Neurosurgery Division, Department of Neurosciences, Geneva University Hospital, Geneva, Switzerland.
6
Department of Imaging and Medical information Sciences, Neuroradiology Division, Geneva University Hospital, Geneva, Switzerland.
7
Laboratory of Tumor immunology, Translational research center for oncohaematology, Department of Internal Medicine Specialties, University of Geneva, & Division of Oncology, HUG, Geneva, Switzerland.

Abstract

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 in HLA-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 MHC class I and 2 MHC class II peptides) i.d. and poly-ICLC i.m. After protocol amendment, IMA950 and poly-ICLC were mixed and injected s.c. (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 CD4 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 Th1 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.

PMID:
30753611
DOI:
10.1093/neuonc/noz040

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