Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients
Denis Migliorini, Valérie Dutoit, Mathilde Allard, Nicole Grandjean Hallez, Eliana Marinari, Valérie Widmer, Géraldine Philippin, Francesca Corlazzoli, Robin Gustave, Mario Kreutzfeldt, Nathalie Blazek, Joëlle Wasem, Andreas Hottinger, Avinash Koka, Shahan Momjian, Alexander Lobrinus, Doron Merkler, Maria-Isabel Vargas, Paul R Walker, Anna Patrikidou, Pierre-Yves Dietrich, Denis Migliorini, Valérie Dutoit, Mathilde Allard, Nicole Grandjean Hallez, Eliana Marinari, Valérie Widmer, Géraldine Philippin, Francesca Corlazzoli, Robin Gustave, Mario Kreutzfeldt, Nathalie Blazek, Joëlle Wasem, Andreas Hottinger, Avinash Koka, Shahan Momjian, Alexander Lobrinus, Doron Merkler, Maria-Isabel Vargas, Paul R Walker, Anna Patrikidou, Pierre-Yves Dietrich
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 (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.
Keywords: IMA950; glioma; immune response; peptide vaccine; poly-ICLC.
© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Source: PubMed