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Brain Tumor Immunotherapy: What have We Learned so Far?

Van Gool SW - Front Oncol (2015)

Bottom Line: High grade glioma is a rare brain cancer, incurable in spite of modern neurosurgery, radiotherapy, and chemotherapy.We learned how to combine immunotherapy with standard multimodal treatment strategies for newly diagnosed glioblastoma multiforme patients.The developmental program allows further improvements related to newest scientific insights.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, KU Leuven , Leuven , Belgium.

ABSTRACT
High grade glioma is a rare brain cancer, incurable in spite of modern neurosurgery, radiotherapy, and chemotherapy. Novel approaches are in research, and immunotherapy emerges as a promising strategy. Clinical experiences with active specific immunotherapy demonstrate feasibility, safety and most importantly, but incompletely understood, prolonged long-term survival in a fraction of the patients. In relapsed patients, we developed an immunotherapy schedule and we categorized patients into clinically defined risk profiles. We learned how to combine immunotherapy with standard multimodal treatment strategies for newly diagnosed glioblastoma multiforme patients. The developmental program allows further improvements related to newest scientific insights. Finally, we developed a mode of care within academic centers to organize cell-based therapies for experimental clinical trials in a large number of patients.

No MeSH data available.


Related in: MedlinePlus

Immunotherapy for HGG: a translational research program.
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Figure 1: Immunotherapy for HGG: a translational research program.

Mentions: Active specific immunotherapy with autologous mature dendritic cells (DCm) loaded with autologous tumor cell lysate (DCm-HGG-L) is an emerging and innovative treatment approach for patients with HGG. The development of DC therapy in HGG has started in 1999 in our center. Since then, we established a complete translational research program from bench to bed (Figure 1) including in vitro experiments (15, 16), in vivo experiments in the GL261 model (17–19), early clinical phase I/II clinical trials as part of the HGG-IMMUNO-2003 cohort comparison trial for relapsed HGG patients (20–26), a phase I/II clinical trial HGG-2006 for patients with newly diagnosed GBM (EudraCT 2006-002881-20) (27, 28), and the recently finished phase IIb prospective placebo-controlled double-blind randomized clinical trial (RCT) HGG-2010 (EudraCT 2009-018228-14). In parallel to this clinical program, advanced MRI studies have been performed on HGG, in particular to characterize immunotherapy-related changes (29–32). In this program, insights from preclinical research were translated into the HGG-IMMUNO-2003 cohort (A–D) comparison trial. Data from these cohorts were then used for integration into the multimodal treatment of patients with primary diagnosis of GBM. As such, the vaccination technology from cohort C was used for the HGG-2006 trial, while the technology from cohort D is now used for the RCT HGG-2010. In parallel, according to the evolving legislation, the preparation for the clinical applications was embedded into a Good Manufacturing Practice (GMP) facility within the University Hospitals Leuven. The translation back from bed to bench has been realized by samplings of tumor tissue and blood samples taken at defined vaccination time points. The new preclinical research perspectives in 2014 include galectin-1 targeting as a strategy for immunomodulation and oncolytic virus therapy.


Brain Tumor Immunotherapy: What have We Learned so Far?

Van Gool SW - Front Oncol (2015)

Immunotherapy for HGG: a translational research program.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4470276&req=5

Figure 1: Immunotherapy for HGG: a translational research program.
Mentions: Active specific immunotherapy with autologous mature dendritic cells (DCm) loaded with autologous tumor cell lysate (DCm-HGG-L) is an emerging and innovative treatment approach for patients with HGG. The development of DC therapy in HGG has started in 1999 in our center. Since then, we established a complete translational research program from bench to bed (Figure 1) including in vitro experiments (15, 16), in vivo experiments in the GL261 model (17–19), early clinical phase I/II clinical trials as part of the HGG-IMMUNO-2003 cohort comparison trial for relapsed HGG patients (20–26), a phase I/II clinical trial HGG-2006 for patients with newly diagnosed GBM (EudraCT 2006-002881-20) (27, 28), and the recently finished phase IIb prospective placebo-controlled double-blind randomized clinical trial (RCT) HGG-2010 (EudraCT 2009-018228-14). In parallel to this clinical program, advanced MRI studies have been performed on HGG, in particular to characterize immunotherapy-related changes (29–32). In this program, insights from preclinical research were translated into the HGG-IMMUNO-2003 cohort (A–D) comparison trial. Data from these cohorts were then used for integration into the multimodal treatment of patients with primary diagnosis of GBM. As such, the vaccination technology from cohort C was used for the HGG-2006 trial, while the technology from cohort D is now used for the RCT HGG-2010. In parallel, according to the evolving legislation, the preparation for the clinical applications was embedded into a Good Manufacturing Practice (GMP) facility within the University Hospitals Leuven. The translation back from bed to bench has been realized by samplings of tumor tissue and blood samples taken at defined vaccination time points. The new preclinical research perspectives in 2014 include galectin-1 targeting as a strategy for immunomodulation and oncolytic virus therapy.

Bottom Line: High grade glioma is a rare brain cancer, incurable in spite of modern neurosurgery, radiotherapy, and chemotherapy.We learned how to combine immunotherapy with standard multimodal treatment strategies for newly diagnosed glioblastoma multiforme patients.The developmental program allows further improvements related to newest scientific insights.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, KU Leuven , Leuven , Belgium.

ABSTRACT
High grade glioma is a rare brain cancer, incurable in spite of modern neurosurgery, radiotherapy, and chemotherapy. Novel approaches are in research, and immunotherapy emerges as a promising strategy. Clinical experiences with active specific immunotherapy demonstrate feasibility, safety and most importantly, but incompletely understood, prolonged long-term survival in a fraction of the patients. In relapsed patients, we developed an immunotherapy schedule and we categorized patients into clinically defined risk profiles. We learned how to combine immunotherapy with standard multimodal treatment strategies for newly diagnosed glioblastoma multiforme patients. The developmental program allows further improvements related to newest scientific insights. Finally, we developed a mode of care within academic centers to organize cell-based therapies for experimental clinical trials in a large number of patients.

No MeSH data available.


Related in: MedlinePlus