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Transient lymphocyte count decrease correlates with oncolytic adenovirus efficacy in humans: mechanistic and
Santeri A Pakola1, James H A Clubb1,2, Tatiana V Kudling1
1Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.
Journal for Immunotherapy of Cancer
|January 27, 2025
Summary
Oncolytic virus TILT-123 therapy increased effector lymphocytes in tumors. Peripheral lymphocyte count decrease shows promise as a biomarker for oncolytic adenovirus therapy response in patients with advanced solid tumors.
Area of Science:
- Oncolytic virotherapy
- Immunotherapy
- Cancer research
Background:
- Oncolytic viruses (OVs) are emerging immunotherapeutics for cold tumors.
- Research on OV mechanisms and biomarkers in humans is limited.
- TILT-123 (igrelimogene litadenorepvec) encodes tumor necrosis alpha and interleukin-2 to enhance T-cell responses.
Purpose of the Study:
- Evaluate immunological effects of TILT-123 in the TUNIMO clinical trial.
- Identify potential biomarkers of response to TILT-123 therapy.
- Gain insights into synergistic combination treatments for advanced solid tumors.
Main Methods:
- Phase I TUNIMO trial treated 20 patients with advanced solid tumors using TILT-123.
- Therapy response assessed via CT, PET scans, and overall survival (OS).
- Biological samples (blood, tumor biopsies) analyzed using immunohistochemistry, transcriptomics, proteomics, and flow cytometry.
Main Results:
- TILT-123 induced cyclical decreases in blood lymphocyte counts, correlating with better response and OS.
- Increased CD8+, CD4+ T cells, and NK cells observed in tumors post-intravenous TILT-123.
- Peripheral lymphocyte decrease linked to immune activation and TILT-123 mRNA presence in tumors.
Conclusions:
- TILT-123 therapy promotes effector lymphocyte accumulation in tumors.
- Peripheral lymphocyte count decrease is a potential biomarker for oncolytic adenovirus therapy response.
