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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

Outline of the phase IIb randomized clinical trial HGG-2010.
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Figure 5: Outline of the phase IIb randomized clinical trial HGG-2010.

Mentions: A prospective placebo-controlled double-blind phase IIb RCT was designed to explore the benefit of immunotherapy as fourth treatment modality to be included within the standard primary treatment strategy for patients with GBM (Figure 5). Supported by our experiences with patients included in HGG-2006, the design of the experimental arm (immunotherapy) is almost similar to HGG-2006. DCm-HGG-L is prepared and maturation is induced similar to Cohort D of the HGG-IMMUNO-2003 trial, using TNF-a, IL-1b, and Imiquimod skin preparation (aimed for TLR7-mediated DC activation). The design of the control arm is the current standard primary treatment: surgery, radiochemotherapy with TMZ, and maintenance chemotherapy with TMZ (3, 4). Randomization is performed with age as stratification variable (99). MGMT (O(6)-methylguanine DNA methyltransferase) methylation is not used for stratification. There is emerging evidence that other cytogenetic abnormalities outside MGMT methylation are of strong prognostic value as well (100–102). Primary endpoint of the trial is the PFS after six cycles of maintenance chemotherapy with TMZ. Secondary endpoints are quality of life assessments, OS, and induction of immune responses in both arms.


Brain Tumor Immunotherapy: What have We Learned so Far?

Van Gool SW - Front Oncol (2015)

Outline of the phase IIb randomized clinical trial HGG-2010.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Outline of the phase IIb randomized clinical trial HGG-2010.
Mentions: A prospective placebo-controlled double-blind phase IIb RCT was designed to explore the benefit of immunotherapy as fourth treatment modality to be included within the standard primary treatment strategy for patients with GBM (Figure 5). Supported by our experiences with patients included in HGG-2006, the design of the experimental arm (immunotherapy) is almost similar to HGG-2006. DCm-HGG-L is prepared and maturation is induced similar to Cohort D of the HGG-IMMUNO-2003 trial, using TNF-a, IL-1b, and Imiquimod skin preparation (aimed for TLR7-mediated DC activation). The design of the control arm is the current standard primary treatment: surgery, radiochemotherapy with TMZ, and maintenance chemotherapy with TMZ (3, 4). Randomization is performed with age as stratification variable (99). MGMT (O(6)-methylguanine DNA methyltransferase) methylation is not used for stratification. There is emerging evidence that other cytogenetic abnormalities outside MGMT methylation are of strong prognostic value as well (100–102). Primary endpoint of the trial is the PFS after six cycles of maintenance chemotherapy with TMZ. Secondary endpoints are quality of life assessments, OS, and induction of immune responses in both arms.

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