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

Migliorini, Denis; Dutoit, Valérie; Allard, Mathilde; Hallez, Nicole Grandjean; Marinari, Eliana; Widmer, Valérie; Philippin, Géraldine; Corlazzoli, Francesca; Gustave, Robin; Kreutzfeldt, Mario; Blazek, N.; Wasem, J.; Hottinger, Andreas F.; Koka, Avinash; Momjian, Shahan; Lobrinus, Alexander; Merkler, Doron; Vargas, Maria-Isabel; Walker, Paul R; Patrikidou, Anna; Dietrich, Pierre‐Yves

doi:10.1093/neuonc/noz040

Cited by 111 publications

(101 citation statements)

References 28 publications

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“…IMA950 is made up of 9 CD8 specific peptides derived from BCAN, CSPG4, FABP7, IGF2BP3, NRCAM, NLGN4X, PTPRZ1, and TNC as well as two CD4 specific peptides derived from survivin and c-met ( 150 ). This multi-peptide vaccine was given in conjunction with the immune boosting adjuvant poly-ICLC to GBM patients in a phase I/II clinical trial ( 111 ). This vaccination was well tolerated by patients and induced antigen specific CD8 + and CD4 + T cell responses ( 111 ).…”

Section: Overcoming Gbm-driven Immunosuppressionmentioning

confidence: 99%

Immune Escape in Glioblastoma Multiforme and the Adaptation of Immunotherapies for Treatment

et al. 2020

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Glioblastoma multiforme (GBM) is the most frequently occurring primary brain tumor and has a very poor prognosis, with only around 5% of patients surviving for a period of 5 years or more after diagnosis. Despite aggressive multimodal therapy, consisting mostly of a combination of surgery, radiotherapy, and temozolomide chemotherapy, tumors nearly always recur close to the site of resection. For the past 15 years, very little progress has been made with regards to improving patient survival. Although immunotherapy represents an attractive therapy modality due to the promising pre-clinical results observed, many of these potential immunotherapeutic approaches fail during clinical trials, and to date no immunotherapeutic treatments for GBM have been approved. As for many other difficult to treat cancers, GBM combines a lack of immunogenicity with few mutations and a highly immunosuppressive tumor microenvironment (TME). Unfortunately, both tumor and immune cells have been shown to contribute towards this immunosuppressive phenotype. In addition, current therapeutics also exacerbate this immunosuppression which might explain the failure of immunotherapy-based clinical trials in the GBM setting. Understanding how these mechanisms interact with one another, as well as how one can increase the anti-tumor immune response by addressing local immunosuppression will lead to better clinical results for immune-based therapeutics. Improving therapeutic delivery across the blood brain barrier also presents a challenge for immunotherapy and future therapies will need to consider this. This review highlights the immunosuppressive mechanisms employed by GBM cancers and examines potential immunotherapeutic treatments that can overcome these significant immunosuppressive hurdles.

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Section: Overcoming Gbm-driven Immunosuppressionmentioning

confidence: 99%

Immune Escape in Glioblastoma Multiforme and the Adaptation of Immunotherapies for Treatment

et al. 2020

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“…PFS was 74% at 6 months and 31% at 9 months [180]. The second clinical trial was a phase 1/2 trial of the IMA950 vaccine adjuvanted with poly-ICLC in high-grade gliomas; CD8 T-cell responses to a single or multiple peptides were observed in 63.2% and 36.8% of patients, respectively, while median OS was 19 months, comparing favourably to classical chemoradiation results [181]. A phase 1/2 trial evaluating the combination of the IMA950 vaccine with pembrolizumab in recurrent GBM is currently ongoing (NCT03665545).…”

Section: Vaccines + Chemotherapymentioning

confidence: 99%

Cancer Vaccines

Henriquez¹,

Arkenau²,

Dutoit³

et al. 2019

Cancer Immunotherapy and Biological Cancer Treatments

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Recent advances in immuno-oncology have allowed for the design of more specific and efficient cancer vaccine approaches. There has been an improvement in molecular biology techniques, as well as a greater understanding of the mechanisms involved in the activation and regulation of T cells and the interplay between the components of the immune system and the escape mechanisms used by cancer cells and the tumour microenvironment. As a result, many interesting developments in therapeutic cancer vaccines are ongoing, with influence on survival still to be proven. The spectrum of tumour antigens that are recognised by T cells is still largely unchartered and, most importantly, dynamically evolving over time, driven by clonal evolution and treatment-driven selection. Vaccine approaches currently in development and tested in clinical studies are based on tumour antigens specifically identified for each tumour type, on tumour cells or dendritic cells, the latter having the potential to be modified to incorporate immunostimulatory genes. However, interplay between the immune system and the tumour and the inhibitory mechanisms developed by tumour cells to subvert immune responses are crucial issues that will need to be targeted in order for efficient therapeutic vaccines to emerge.

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“…Authors were able to confirm the immunogenicity, as well as show the promising patient outcomes, as four out of six patients did not experience recurrence after 25 months, and, in the remaining two cases, there was complete tumor regression after therapy with anti-PD-1. In cases of trials involving glioblastoma, which shows a substantially lower level of mutations, there was a detectable immune response, as shown by the presence of neoantigen-specific lymphocytes [10] and tumor-infiltrating lymphocytes [11]. Remarkably, Migliorini et al [10] used antigen sequences which were directly derived from mass spectrometry-based immunopeptidome sequencing.…”

Section: Introduction: Neoantigens In Cancer Immunotherapymentioning

confidence: 99%

“…In cases of trials involving glioblastoma, which shows a substantially lower level of mutations, there was a detectable immune response, as shown by the presence of neoantigen-specific lymphocytes [10] and tumor-infiltrating lymphocytes [11]. Remarkably, Migliorini et al [10] used antigen sequences which were directly derived from mass spectrometry-based immunopeptidome sequencing. In all published cases, the vaccines were well tolerated by patients.…”

Section: Introduction: Neoantigens In Cancer Immunotherapymentioning

confidence: 99%

Mass Spectrometry-Based Identification of MHC-Associated Peptides

Kote

Piróg

Bedran

et al. 2020

Cancers

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Neoantigen-based immunotherapies promise to improve patient outcomes over the current standard of care. However, detecting these cancer-specific antigens is one of the significant challenges in the field of mass spectrometry. Even though the first sequencing of the immunopeptides was done decades ago, today there is still a diversity of the protocols used for neoantigen isolation from the cell surface. This heterogeneity makes it difficult to compare results between the laboratories and the studies. Isolation of the neoantigens from the cell surface is usually done by mild acid elution (MAE) or immunoprecipitation (IP) protocol. However, limited amounts of the neoantigens present on the cell surface impose a challenge and require instrumentation with enough sensitivity and accuracy for their detection. Detecting these neopeptides from small amounts of available patient tissue limits the scope of most of the studies to cell cultures. Here, we summarize protocols for the extraction and identification of the major histocompatibility complex (MHC) class I and II peptides. We aimed to evaluate existing methods in terms of the appropriateness of the isolation procedure, as well as instrumental parameters used for neoantigen detection. We also focus on the amount of the material used in the protocols as the critical factor to consider when analyzing neoantigens. Beyond experimental aspects, there are numerous readily available proteomics suits/tools applicable for neoantigen discovery; however, experimental validation is still necessary for neoantigen characterization.

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

Cited by 111 publications

References 28 publications

Immune Escape in Glioblastoma Multiforme and the Adaptation of Immunotherapies for Treatment

Immune Escape in Glioblastoma Multiforme and the Adaptation of Immunotherapies for Treatment

Cancer Vaccines

Mass Spectrometry-Based Identification of MHC-Associated Peptides

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