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Oncolytic adenoviruses for treatment of brain tumours
C M F Dirven1, V W van Beusechem, M L M Lamfers
1Department of Medical Oncology, Division of Gene Therapy, VU University Medical Centre, Amsterdam, The Netherlands. c.dirven@vumc.nl
Abstract:
Standard therapies are not capable of curing patients with malignant glioma; more than 90% of patients die within 2 years after diagnosis. Gene therapy appeared as a promising new approach for this disease. However, results of clinical trials with replication deficient viral vectors were disappointing. The main reasons being poor transduction efficiency of adenovirus towards glioma cells and limited spread and distribution of the vector in the tumour. With the increasing knowledge of viral genetics and its functions, an attractive alternative tool to kill malignant glioma cells has been developed: Replicating adenovirus as an oncolytic agent. This type of therapy, also referred to as virotherapy, has the potential to overcome some of the limitations connected with replication deficient adenoviral vectors. In this review the authors describe the latest developments in strategies that are being used to create a tumour- or glioma-selective replicating adenovirus. Special attention is given to the methods of viral delivery to an infiltrating tumour in the brain, regarding optimal dose and toxicity. Furthermore, the role of conventional antitumour treatments, such as irradiation and chemotherapy, in enhancing the effect of virotherapy is being emphasised.
Insights
Replicating adenoviruses offer a promising oncolytic virotherapy for malignant glioma, overcoming limitations of traditional gene therapy. This approach enhances tumor cell killing and can be combined with standard treatments for better outcomes.
Area of Science:
- Oncology
- Virology
- Gene Therapy
Background:
- Malignant glioma has a poor prognosis with standard therapies, necessitating novel treatment approaches.
- Previous gene therapy trials using replication-deficient adenoviruses showed limited efficacy due to poor transduction and vector spread.
- Replicating adenoviruses present an alternative oncolytic strategy for glioma treatment.
Purpose of the Study:
- To review advancements in developing tumor-selective replicating adenoviruses for malignant glioma.
- To discuss strategies for effective viral delivery, optimal dosing, and toxicity management in brain tumors.
- To highlight the synergistic potential of virotherapy with conventional treatments like irradiation and chemotherapy.
Main Methods:
- Review of current research on replicating adenovirus development for glioma.
- Analysis of viral delivery methods for brain tumors.
- Evaluation of combination strategies with standard cancer therapies.
Main Results:
- Replicating adenoviruses demonstrate potential as oncolytic agents against malignant glioma.
- Strategies are emerging to enhance glioma selectivity and improve viral spread within tumors.
- Combined modality treatments show promise for enhanced therapeutic effects.
Conclusions:
- Replicating adenovirus-based virotherapy is a promising strategy for malignant glioma.
- Optimizing viral delivery and selectivity is crucial for clinical success.
- Combination with conventional therapies may improve treatment efficacy and patient outcomes.