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Published on: January 15, 2016
A Comparative Study of Replication-Incompetent and -Competent Adenoviral Therapy-Mediated Immune Response in a Murine
Julius W Kim1, Jason Miska1, Jacob S Young2
1Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Abstract:
Oncolytic virotherapy is a treatment approach with increasing clinical relevance, as indicated by the marked survival benefit seen in animal models and its current exploration in human patients with cancer. The use of an adenovirus vector for this therapeutic modality is common, has significant clinical benefit in animals, and its efficacy has recently been linked to an anti-tumor immune response that occurs following tumor antigen presentation. Here, we analyzed the adaptive immune system's response following viral infection by comparing replication-incompetent and replication-competent adenoviral vectors. Our findings suggest that cell death caused by replication-competent adenoviral vectors is required to induce a significant anti-tumor immune response and survival benefits in immunocompetent mice bearing intracranial glioma. We observed significant changes in the repertoire of immune cells in the brain and draining lymph nodes and significant recruitment of CD103+ dendritic cells (DCs) in response to oncolytic adenoviral therapy, suggesting the active role of the immune system in anti-tumor response. Our data suggest that the response to oncolytic virotherapy is accompanied by local and systemic immune responses and should be taken in consideration in the future design of the clinical studies evaluating oncolytic virotherapy in patients with glioblastoma multiforme (GBM).
Insights
Replication-competent adenoviral vectors induce significant anti-tumor immune responses and survival benefits in glioma models. This oncolytic virotherapy approach requires cell death to activate the immune system for cancer treatment.
Area of Science:
- Oncology
- Immunology
- Virology
Background:
- Oncolytic virotherapy is a promising cancer treatment.
- Adenovirus vectors are commonly used for virotherapy.
- Efficacy is linked to anti-tumor immune responses.
Purpose of the Study:
- Compare immune response to replication-incompetent vs. replication-competent adenoviral vectors.
- Analyze adaptive immune system changes following viral infection.
- Investigate the role of cell death in oncolytic virotherapy efficacy.
Main Methods:
- Infection of immunocompetent mice with glioma using different adenoviral vectors.
- Analysis of immune cell populations in the brain and lymph nodes.
- Assessment of immune cell recruitment, including dendritic cells.
Main Results:
- Replication-competent adenoviral vectors induced significant anti-tumor immune responses and survival benefits.
- Cell death mediated by replication-competent vectors is crucial for efficacy.
- Significant changes in immune cell repertoire and recruitment of CD103+ dendritic cells were observed.
Conclusions:
- Oncolytic virotherapy with replication-competent adenoviral vectors requires cell death for anti-tumor immunity.
- The anti-tumor response involves local and systemic immune activation.
- Findings inform future clinical trial designs for glioblastoma multiforme (GBM).
