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Updated: May 20, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Optimization and preclinical design of genetically engineered viruses for human oncolytic therapy
Donavon C Hiss1, Burtram C Fielding
1University of the Western Cape, Department of Medical Biosciences, Molecular Oncology Research Laboratory, Bellville, 7535, South Africa. dhiss@uwc.ac.za
Introduction:
Oncolytic viruses (OVs) occupy a strategic niche in the dynamic era of biological and gene therapy of human cancers. However, the use of OVs is the subject of close scrutiny due to impediments such as the insufficiency of patient generalizations posed by heterogeneous tumor responses to treatment, inherent or potentially lethal viral pathogenicities, unanticipated host- or immune-related adverse effects, and the emergence of virus-resistant cancer cells. These challenges can be overcome by the design and development of more definitive (optimized, targeted, and individualized) cancer virotherapeutics.
Areas Covered:
The translation of current knowledge and recent innovations into rational treatment prospects hinges on an iterative loop of variables pertaining to genetically engineered viral oncolytic efficacy and safety profiles, mechanism-of-action data, potencies of synergistic oncolytic viral combinations with conventional tumor, immuno-, chemo-, and radiation treatment modalities, optimization of the probabilities of treatment successes in heterogeneous (virus-sensitive and -resistant) tumor cell populations by mathematical modeling, and lessons learned from preclinical studies and human clinical trials.
Expert Opinion:
In recent years, it has become increasingly clear that proof-of-principle is critical for the preclinical optimization of oncolytic viruses to target heterogeneous forms of cancer and to prioritize current concerns related to the efficacy and safety of oncolytic virotherapy.
Insights
Optimizing oncolytic viruses (OVs) for cancer therapy requires addressing challenges like tumor heterogeneity and safety. Preclinical development must focus on efficacy and safety for improved cancer virotherapeutics.
Area of Science:
- Oncolytic virotherapy
- Cancer gene therapy
- Biological cancer treatment
Background:
- Oncolytic viruses (OVs) offer a promising approach in cancer biological and gene therapy.
- Key challenges include heterogeneous tumor responses, viral pathogenicity, adverse effects, and virus resistance.
- Developing optimized, targeted, and individualized cancer virotherapeutics is crucial.
Purpose of the Study:
- To highlight the critical need for preclinical optimization of oncolytic viruses.
- To address current concerns regarding the efficacy and safety of oncolytic virotherapy.
- To guide the development of more effective cancer treatments.
Main Methods:
- Evaluating genetically engineered viral efficacy and safety profiles.
- Investigating mechanisms of action and synergistic combinations with conventional therapies.
- Utilizing mathematical modeling for treatment success optimization in heterogeneous tumors.
- Incorporating lessons from preclinical studies and human clinical trials.
Main Results:
- Proof-of-principle is essential for preclinical optimization.
- Addressing tumor heterogeneity is critical for successful OV application.
- Balancing efficacy and safety is paramount for clinical translation.
Conclusions:
- Preclinical optimization is vital for targeting diverse cancers with OVs.
- Prioritizing efficacy and safety concerns is key to advancing oncolytic virotherapy.
- Further research is needed to overcome current limitations and enhance patient outcomes.
