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

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...

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Published in:	Neuro-oncology (Charlottesville, Va.) Vol. 21; no. 7; pp. 923 - 933
Main Authors:	Migliorini, Denis, Dutoit, Valérie, Allard, Mathilde, Grandjean Hallez, Nicole, Marinari, Eliana, Widmer, Valérie, Philippin, Géraldine, Corlazzoli, Francesca, Gustave, Robin, Kreutzfeldt, Mario, Blazek, Nathalie, Wasem, Joëlle, Hottinger, Andreas, Koka, Avinash, Momjian, Shahan, Lobrinus, Alexander, Merkler, Doron, Vargas, Maria-Isabel, Walker, Paul R, Patrikidou, Anna, Dietrich, Pierre-Yves
Format:	Journal Article
Language:	English
Published:	US Oxford University Press 11-07-2019
Subjects:	Adult Aged Astrocytoma - immunology Astrocytoma - pathology Astrocytoma - therapy Cancer Vaccines - administration & dosage Carboxymethylcellulose Sodium - administration & dosage Carboxymethylcellulose Sodium - analogs & derivatives CD8-Positive T-Lymphocytes - immunology Chemoradiotherapy - mortality Clinical Investigations Combined Modality Therapy Female Follow-Up Studies Glioblastoma - immunology Glioblastoma - pathology Glioblastoma - therapy Humans Male Middle Aged Peptides - administration & dosage Poly I-C - administration & dosage Polylysine - administration & dosage Polylysine - analogs & derivatives Prognosis Survival Rate Vaccines, Subunit - administration & dosage Young Adult poly-ICLC glioma IMA950 peptide vaccine immune response
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 First co-authors
ISSN:	1522-8517 1523-5866
DOI:	10.1093/neuonc/noz040