Related Experiment Video
Updated: Jun 27, 2025
Patient-Derived Tumor Explants As a "Live" Preclinical Platform for Predicting Drug Resistance in Patients
Published on: February 7, 2021
Patient-derived tumoroids and proteomic signatures: tools for early drug discovery
Hélène Lê1,2, Jules Deforges1, Pasquale Cutolo3
1Transgene S.A., Illkirch-Graffenstaden, France.
Abstract:
Onco-virotherapy is an emergent treatment for cancer based on viral vectors. The therapeutic activity is based on two different mechanisms including tumor-specific oncolysis and immunostimulatory properties. In this study, we evaluated onco-virotherapy in vitro responses on immunocompetent non-small cell lung cancer (NSCLC) patient-derived tumoroids (PDTs) and healthy organoids. PDTs are accurate tools to predict patient's clinical responses at the in vitro stage. We showed that onco-virotherapy could exert specific antitumoral effects by producing a higher number of viral particles in PDTs than in healthy organoids. In the present work, we used multiplex protein screening, based on proximity extension assay to highlight different response profiles. Our results pointed to the increase of proteins implied in T cell activation, such as IFN-γ following onco-virotherapy treatment. Based on our observation, oncolytic viruses-based therapy responders are dependent on several factors: a high PD-L1 expression, which is a biomarker of greater immune response under immunotherapies, and the number of viral particles present in tumor tissue, which is dependent to the metabolic state of tumoral cells. Herein, we highlight the use of PDTs as an alternative in vitro model to assess patient-specific responses to onco-virotherapy at the early stage of the preclinical phases.
Insights
Onco-virotherapy shows promise for non-small cell lung cancer (NSCLC) treatment. Patient-derived tumoroids (PDTs) effectively model responses, revealing viral particle production and T cell activation markers like IFN-γ.
Area of Science:
- Oncology
- Virology
- Immunotherapy
Background:
- Onco-virotherapy utilizes viral vectors for cancer treatment, leveraging tumor lysis and immune stimulation.
- Patient-derived tumoroids (PDTs) offer a preclinical in vitro model for predicting patient responses.
- Non-small cell lung cancer (NSCLC) remains a significant global health challenge.
Purpose of the Study:
- To evaluate in vitro responses of onco-virotherapy in NSCLC patient-derived tumoroids (PDTs) and healthy organoids.
- To identify biomarkers and factors influencing onco-virotherapy efficacy.
- To establish PDTs as a predictive model for onco-virotherapy outcomes.
Main Methods:
- Culturing of immunocompetent NSCLC PDTs and healthy organoids.
- Onco-virotherapy treatment and assessment of viral particle production.
- Multiplex protein screening using proximity extension assay (PEA).
Main Results:
- Onco-virotherapy demonstrated specific anti-tumoral effects with higher viral particle replication in PDTs compared to healthy organoids.
- Treatment led to increased expression of T cell activation proteins, including Interferon-gamma (IFN-γ).
- PD-L1 expression and viral particle load, influenced by tumor cell metabolism, were identified as key response factors.
Conclusions:
- PDTs are a valuable in vitro model for assessing patient-specific responses to onco-virotherapy.
- Oncolytic virus efficacy is linked to PD-L1 expression and viral replication dynamics within the tumor microenvironment.
- This study supports the use of PDTs in early preclinical phases for onco-virotherapy development.
