DCVax®-L—Developed by Northwest Biotherapeutics

Polyzoidis, Stavros; Ashkan, Keyoumars

doi:10.4161/hv.29276

Cited by 60 publications

(38 citation statements)

References 51 publications

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“…The same group investigated the integration of DC vaccine into the standard treatment of patients with newly-diagnosed GBM and achieved an unexpected median OS of 24 months (116). Another large double-blinded randomized phase II trial of DC vaccine (DCVax-L) in patients with newly diagnosed GBM also showed encouraging results, with a median OS of 3 years, with 4-year survival reaching 33%, and 27% of patients exceeding 6-year survival from initial surgery (117,118). However, the clarification of these promising results with DC vaccine strategies are essential in well-designed randomized phase III clinical trials, such as the DCVax-L phase III study (NCT00045968) which is now ongoing and whose final results are eagerly awaited.…”

Section: Immunotherapy Of Gbmmentioning

confidence: 90%

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

et al. 2017

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Abstract. Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis. A number of targeted anticancer drugs, such as small-molecule kinase inhibitors and monoclonal antibodies, have been evaluated in clinical trials with newly-diagnosed, as well as recurrent GBM. Unfortunately, to date, only a single antiangiogenic agent, bevacizumab, has been approved for the treatment of recurrent GBM in the USA and Canada. The novel possibilities of cancer immunotherapy, especially immune checkpoint inhibitors, are being evaluated in clinical trials of patients with GBM. The most recent clinical experiences with targeted therapy as well as immunotherapy of GBM are given in this review. The relative lack of success of some of these approaches recently revealed in well-designed randomized clinical trials is also discussed.Glioblastoma multiforme (GBM) belongs to the largest group of primary central nervous system (CNS) tumors, so-called gliomas, which are formed from supporting glial cells in the brain parenchyma (1, 2). GBM represents the most common and most malignant tumor in this class, with an incidence of 3-4/100,000/year (3, 4). GBM is an extremely invasive and difficult to treat tumor, characterized by intense and aberrant vascularization and high resistance to radiotherapy (RT) and chemotherapy (CHT). The current standard of care for patients with newly-diagnosed GBM comprises of neurosurgery and subsequent concomitant chemoradiotherapy by fractionated external-beam RT and systemic temozolomide followed by systemic temozolomide in the adjuvant setting (5). There are only very limited possibilities for the treatment of subsequent recurrences, generally with minimal clinical efficacy (6). Despite intensive multimodal treatment strategies, the median survival of patients with GBM is still 12.1-14.6 months and only 3-5% of patients survive longer than 3 years (7).Enormous progress has been made in the genetics and epigenetics of GBM during the past decade. The Cancer 21Τhis article is freely accessible online.Correspondence to: Jiri Polivka, Department of Neurology, Faculty Hospital Plzen, alej Svobody 80, 304 60, Plzen, Czech Republic. E-mail: polivka@fnplzen.cz Key Words: Glioblastoma multiforme, GBM, targeted therapy, immunotherapy, immune checkpoint inhibitors, PD1 inhibition, CTLA4 inhibition, clinical trials, personalized medicine, review. ANTICANCER RESEARCH 37: 21-34 (2017) [8][9][10][11][12]. The most important genetic...

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Section: Immunotherapy Of Gbmmentioning

confidence: 90%

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

et al. 2017

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“…Improved outcome appeared also to stratify by tumor molecular subtype as measured by gene expression profiling, with increased survival shown for patients within the mesenchymal subgroup of glioblastoma [11]. Currently, a Phase III multi-center trial of DC vaccination for newly diagnosed glioblastoma is underway, with approximately 348 patients to be enrolled (NCT00045968) [19].…”

Section: Acid-eluted Peptide DC Vaccinementioning

confidence: 98%

Dendritic cell immunotherapy for brain tumors

2015

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Glioblastomas are characterized by immunosuppression, rapid proliferation, angiogenesis, and invasion into the surrounding brain parenchyma. Limitations in current therapeutic approaches have spurred the development of personalized, patient-specific treatments. Among these, active immunotherapy has emerged as a viable option for glioma treatment. The ability to generate an immune response utilizing patient-derived dendritic cells (DCs) (professional antigen-presenting cells) is especially attractive. This approach to glioma treatment allows for the immunologic targeting and destruction of malignant cells. Data acquired in multiple pre-clinical models and clinical trials have shown significant responses and prolonged survival. Here we provide an overview of the current status of DC vaccination for the treatment of gliomas.

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“…In their report to the European Parliament and the Council in March 2014, the reporters from the European Commission pointed to creating a more favorable environment for ATMP developers working in an academic or non-for-profit setting, including by promoting early contacts with the authorities through the application of the fee reduction for scientific advice and by extending the existing certification scheme to these developers (144). Nevertheless, the DCVax ® -L vaccine is developed by Northwest Biotherapeutics as an adjunct to the treatment of GBM, and is currently under evaluation in a phase III trial (145).…”

Section: Modulation To Escape Immune Evasion Mechanismsmentioning

confidence: 99%

Brain tumor immunotherapy. What have we learned so far?

2015

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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.

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DCVax®-L—Developed by Northwest Biotherapeutics

Cited by 60 publications

References 51 publications

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

Dendritic cell immunotherapy for brain tumors

Brain tumor immunotherapy. What have we learned so far?

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