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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Oncolytic virotherapy: basic principles, recent advances and future directions
Danni Lin1,2,3,4, Yinan Shen1,2,3,4, Tingbo Liang5,6,7,8,9
1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Abstract:
Oncolytic viruses (OVs) have attracted growing awareness in the twenty-first century, as they are generally considered to have direct oncolysis and cancer immune effects. With the progress in genetic engineering technology, OVs have been adopted as versatile platforms for developing novel antitumor strategies, used alone or in combination with other therapies. Recent studies have yielded eye-catching results that delineate the promising clinical outcomes that OVs would bring about in the future. In this review, we summarized the basic principles of OVs in terms of their classifications, as well as the recent advances in OV-modification strategies based on their characteristics, biofunctions, and cancer hallmarks. Candidate OVs are expected to be designed as "qualified soldiers" first by improving target fidelity and safety, and then equipped with "cold weapons" for a proper cytocidal effect, "hot weapons" capable of activating cancer immunotherapy, or "auxiliary weapons" by harnessing tactics such as anti-angiogenesis, reversed metabolic reprogramming and decomposing extracellular matrix around tumors. Combinations with other cancer therapeutic agents have also been elaborated to show encouraging antitumor effects. Robust results from clinical trials using OV as a treatment congruously suggested its significance in future application directions and challenges in developing OVs as novel weapons for tactical decisions in cancer treatment.
Insights
Oncolytic viruses (OVs) are engineered to directly destroy cancer cells and stimulate immune responses. Advances in genetic engineering enable OV modification for enhanced safety, efficacy, and combination therapies against cancer.
Area of Science:
- Oncolytic virotherapy
- Cancer immunotherapy
- Genetic engineering
Background:
- Oncolytic viruses (OVs) are gaining prominence for their dual action: direct tumor cell lysis and modulation of the anti-cancer immune response.
- Genetic engineering advancements have transformed OVs into adaptable platforms for novel anti-cancer strategies, applicable as monotherapy or in combination regimens.
- Recent clinical studies highlight the significant therapeutic potential of OVs in oncology.
Purpose of the Study:
- To review the fundamental principles, classifications, and recent advancements in oncolytic virus modification strategies.
- To explore how OV characteristics, biofunctions, and cancer hallmarks inform engineering approaches.
- To discuss the integration of OVs with other therapeutic modalities for enhanced anti-tumor effects.
Main Methods:
- Classification of oncolytic viruses based on their biological properties and mechanisms of action.
- Analysis of recent strategies for modifying OVs to improve target specificity, safety, and therapeutic efficacy.
- Review of preclinical and clinical data on OV applications, including combination therapies.
Main Results:
- Engineered OVs can be optimized for improved tumor targeting and safety ('qualified soldiers').
- OVs can be equipped with 'weapons' for direct cell killing ('cold weapons'), immune activation ('hot weapons'), or auxiliary functions like anti-angiogenesis and extracellular matrix degradation.
- Combination therapies involving OVs demonstrate promising synergistic anti-tumor effects.
Conclusions:
- Oncolytic viruses represent a significant advancement in cancer treatment, offering versatile platforms for therapeutic innovation.
- Strategic modification and combination with other agents are crucial for maximizing OV efficacy.
- Further clinical development and strategic application are essential to fully realize the potential of OVs in cancer therapy.
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