ArticleClinical pharmacokinetics2025
Role of Antidrug Antibodies in Oncolytic Viral Therapy: A Dynamic Modelling Approach in Cancer Patients Treated with V937 Alone or in Combination.
Article in Clinical pharmacokinetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Oncolytic virus therapy for osteosarcoma: mechanisms, opportunities, and challenges.Frontiers in immunology · 2025Review
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Authors and funding
3 authors.
Funding
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Abstract
BACKGROUND AND
objectiveOncolytic viruses (OVs) are a growing immuno-oncology therapeutic class that rely on their capability to activate the dormant endogenous anti-tumor immune response in order to control or eradicate tumor cells. Given their intrinsic mechanisms of action and their biological nature, development of antidrug antibodies (ADA) represents an important aspect to consider during clinical evaluation. ADAs can potentially affect viral kinetics and/or dynamics, ultimately resulting in reductions or even loss of drug efficacy. Here, we present a semi-mechanistic pharmacokinetic/pharmacodynamic model characterizing the interplay between V937 and neutralizing ADA in cancer patients receiving the V937 oncolytic virus.
methodsThe quantitative framework has been developed integrating viral load and ADA titers from 208 cancer patients who received V937 following intratumoral or intravascular administration, in monotherapy or in combination with pembrolizumab.
resultsThe model successfully captured both V937 time course and the dynamics of ADAs under the different settings, showing no meaningful impact of ADAs on viral kinetics. Moreover, tumor response was neither affected by the preexistence or development of ADAs, which can be explained by the primary role of the immune system in the response.
conclusionsThis quantitative and (semi-) mechanistic framework can be expanded to other oncolytic viruses and used to explore under which scenarios a relevant impact could be observed, thus supporting the development of novel oncolytic viral therapies.
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