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Assessment of current virotherapeutic application schemes: "hit hard and early" versus "killing softly"?
Benjamin Ruf1, Ulrich M Lauer1
1Department of Internal Medicine I, University Hospital Tuebingen , Tuebingen, Germany.
Abstract:
Over the past two decades, a considerable amount of oncolytic vector families has entered numerous clinical trials. However, to this date, the field has not yet been able to come to a common understanding regarding the best possible ways to administer oncolytic viruses to cancer patients. This is mainly due to the fact that so far clinical trials being designed for head-to-head comparisons (such as using two different virotherapeutics originating from two distinct virus families being applied via identical routes in the same types of cancer) are still missing. Hence, there is no consent (i) on the best route of virotherapeutics administration (e.g., systemic versus intratumoral), (ii) on the virus dosages to be applied, (iii) on dosing intervals, and (iv) on the numbers of repetitive courses of virus administration. As the detailed comparison of clinical virotherapy trial regimens is time-consuming and complex, we here present an overview of current state-of-the-art virotherapeutic application schemes. Notably, our comprehensive assessment culminates in raising two rough classifications of virotherapeutic strategies, i.e., "hit hard and early" versus "killing softly". In order to find out which one of these two gross alternatives might be most successful for each and every tumor entity, we here suggest the implementation of phase 1/2 studies, which primarily aim at a repetitive sampling and analysis of tumor samples in cancer patients treated with oncolytic viruses reading out (i) virus-specific, (ii) tumor-specific as well as (iii) immunotherapeutic parameters. On this basis, a rational design of significantly improved virotherapeutic application schemes should be possible in the future.
Insights
Oncolytic virus therapy lacks standardized administration protocols. This review outlines current strategies and proposes "hit hard and early" versus "killing softly" approaches, advocating for Phase 1/2 studies to optimize cancer treatment.
Area of Science:
- Oncology
- Virology
- Clinical Trial Design
Background:
- Oncolytic virus therapy has advanced significantly, with numerous vector families entering clinical trials over the past two decades.
- Despite progress, a consensus on optimal oncolytic virus administration strategies for cancer patients remains elusive.
- Key areas of disagreement include administration routes (systemic vs. intratumoral), virus dosages, dosing intervals, and the number of treatment courses.
Purpose of the Study:
- To provide an overview of current state-of-the-art oncolytic virotherapeutic application schemes.
- To address the lack of head-to-head comparisons in clinical trials for different oncolytic virus strategies.
- To propose a framework for optimizing future oncolytic virotherapy regimens.
Main Methods:
- Comprehensive assessment and overview of existing clinical virotherapy trial regimens.
- Classification of virotherapeutic strategies into two broad categories: "hit hard and early" and "killing softly".
- Recommendation for the implementation of Phase 1/2 studies with repetitive tumor sampling and analysis.
Main Results:
- Identified a lack of standardized protocols for oncolytic virus administration in clinical practice.
- Proposed two distinct conceptual approaches to virotherapy: "hit hard and early" and "killing softly".
- Highlighted the need for detailed analysis of virus-specific, tumor-specific, and immunotherapeutic parameters.
Conclusions:
- Further research and standardized comparisons are crucial for determining the most effective oncolytic virus administration strategies.
- Phase 1/2 studies incorporating comprehensive patient and tumor sampling are recommended for rational design of future regimens.
- Optimizing oncolytic virotherapy application schemes will enhance treatment efficacy for various cancer entities.
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