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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Arenavirus Therapy in Combination with Checkpoint Blockade as an Effective Way for Better Tumour Clearance
Hilal Bhat1,2, Murtaza Ali3, Thamer A Hamdan3
1Institute of Immunology, University of Duisburg-Essen, Essen, Germany, hilal.bhat@uk-koeln.de.
Abstract:
Viruses have been widely used to treat cancer for many years and they achieved tremendous success in clinical trials with outstanding results, which has led to the foundation of companies that develop recombinant viruses for a better tumor treatment. Even though there has been a great progress in the field of viral tumor immunotherapy, until now only one virus, the oncolytic virus talimogene laherparepvec (TVEC), a genetically modified herpes simplex virus type 1 (T-VEC), has been approved by the FDA for cancer treatment. Although oncolytic viruses showed progress in certain cancer types and patient populations but they have yet shown limited efficacy when it comes to solid tumors. Only recently it was demonstrated that the immune stimulatory aspect of oncolytic viruses can strongly contribute to their anti-tumoral activity. One specific example in this context are arenaviruses, which have been shown to be non-cytopathic in nature lead to the massive immune activation within the tumor resulting in strong anti-tumoral activity. This strong immune activation might be also linked to their noncytopathic features, as their immune stimulatory potential is not self-limiting as is the case for oncolytic viruses due to their fast eradication by anti-viral immune effects. Because of this strong immune activation, arenaviruses appear superior to oncolytic viruses when it comes to potent and long-lasting anti-tumor effects in a broad variety of tumor types. Currently one of the most promising therapeutics which has turned to be very much beneficial for the treatment of different cancer types is represented by antibodies targeting checkpoint inhibitors such as PD-1/PD-L-1. In this review, we will summarize anti-tumoral effects of arenaviruses, and will discuss their potential to be combined with checkpoint inhibitors for a more efficient tumor treatment, which further emphasizes that arenavirus therapy as a viroimmunotherapy can be an efficient tool for the better clearance of tumors.
Insights
Arenaviruses, a type of virus, show strong anti-tumor effects by activating the immune system, potentially outperforming oncolytic viruses for cancer immunotherapy. Combining arenavirus therapy with checkpoint inhibitors may offer more effective tumor treatment.
Area of Science:
- Oncology
- Virology
- Immunotherapy
Background:
- Viruses are utilized in cancer treatment, with talimogene laherparepvec (T-VEC) being the only FDA-approved oncolytic virus.
- Oncolytic viruses have limitations, particularly in solid tumors, despite progress in viral tumor immunotherapy.
- The immune-stimulatory properties of viruses are increasingly recognized for their anti-tumoral activity.
Purpose of the Study:
- To review the anti-tumoral effects of arenaviruses.
- To explore the potential of combining arenavirus therapy with checkpoint inhibitors for enhanced cancer treatment.
- To highlight arenavirus therapy as a promising viroimmunotherapy approach.
Main Methods:
- Review of existing literature on arenaviruses and their anti-tumoral mechanisms.
- Analysis of the immune-stimulatory aspects of non-cytopathic viruses like arenaviruses.
- Discussion of combination strategies with immune checkpoint inhibitors (e.g., PD-1/PD-L1).
Main Results:
- Arenaviruses, being non-cytopathic, induce significant immune activation within tumors, leading to potent anti-tumoral activity.
- This immune activation is potentially more sustained than with cytopathic oncolytic viruses.
- Arenaviruses demonstrate potential for broad efficacy across various tumor types.
Conclusions:
- Arenaviruses exhibit superior potential for potent and long-lasting anti-tumor effects compared to traditional oncolytic viruses.
- Combining arenavirus therapy with checkpoint inhibitors represents a promising strategy for improving cancer treatment efficacy.
- Arenavirus-based viroimmunotherapy offers an efficient approach for tumor clearance.
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