ArticleJournal for immunotherapy of cancer2025
Transient lymphocyte count decrease correlates with oncolytic adenovirus efficacy in humans: mechanistic and biomarker findings from TUNIMO phase I trial.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04695327 (A Phase 1, Open-Label, Dose-escalation Clinical Trial of Tumor Necrosis Factor Alpha and Interleukin-2 Coding Oncolytic Adenovirus), which is not on this map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1, Open-Label, Dose-escalation Clinical Trial of Tumor Necrosis Factor Alpha and Interleukin-2 Coding Oncolytic Adenovirus (TILT-123) in Patients With Injectable Solid Tumors
Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Efficacy of oncolytic virus in the treatment of intermediate-to-advanced solid tumors: a systematic review and meta-analysis.Journal of virology · 2025Pooled it
- Recent Advances in Tumor-Infiltrating Lymphocyte Therapy for Melanoma.Current treatment options in oncology · 2026Review
- Immune-cytokine signature predicts survival in patients with advanced melanoma treated with oncolytic adenovirus TILT-123 and chemotherapy and IL-2-free adoptive TIL therapy.Journal for immunotherapy of cancer · 2026Article
- Recent advances in oncolytic virotherapy: insights from clinical trials and combination treatment strategies.Virology journal · 2026Review
- Dyslipidemia-associated natural IgM improves oncolytic virus TILT-123 efficacy through antibody-dependent enhancement in solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Bridging mechanism and clinic: unlocking the full potential of oncolytic virus-based immunotherapy.Molecular cancer · 2026Review
- Oncolytic Virus VV-GMCSF-Lact and Human GM-CSF Against GL261 Glioma in Immunocompetent Mice.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Immuno-oncology recapitulates ontogeny: Modern cell and gene therapy for cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Synergy of oncolytic adenovirus and immune checkpoint inhibitors: transforming cancer immunotherapy paradigms.Frontiers in immunology · 2025Review
- Oncolytic virus therapy in the elderly: immune frailty, challenges, and perspectives.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOncolytic viruses (OVs) are promising immunotherapeutics to treat immunologically cold tumors. However, research on the mechanism of action of OVs in humans and clinically relevant biomarkers is still sparse. To induce strong T-cell responses against solid tumors, TILT-123 (Ad5/3-E2F-d24-hTNFa-IRES-hIL2, igrelimogene litadenorepvec) was developed. TILT-123 encodes two transgenes: tumor necrosis alpha (TNFa) and interleukin-2 (IL-2). TUNIMO (NCT04695327) was a phase I clinical trial using TILT-123 in patients with advanced solid tumors aiming to assess the safety, efficacy, and immunological effects of TILT-123. Research presented in this study evaluated the immunological effects of TILT-123 in the TUNIMO trial by using biological samples collected from the patients during the study, with an objective to leverage the findings to develop possible biomarkers of response and gain insights into possible synergistic combination treatments.
methods20 patients with advanced solid tumors were treated with TILT-123. Response to therapy was assessed with contrast-enhanced CT and fluorodeoxyglucose positron emission tomography, along with overall survival (OS) calculation. Biological samples from patients were collected in the form of blood and tumor biopsies. Collected samples were analyzed with immunohistochemistry, transcriptomics, proteomics, and flow cytometry.
resultsTILT-123 induced cyclical decreases in blood lymphocyte count, and more substantial blood lymphocyte count correlated with better radiographical response and longer OS. Lymphocyte count findings were confirmed with external control dataset of 96 patients. More substantial lymphocyte count change was linked to stronger immune activation in plasma proteome after intravenous TILT-123 and the presence of TILT-123 mRNA in tumors. Regarding other assays. tumor biopsies profiled showed increased amounts of CD8+ T cells, CD4+ T cells and NK cells after intravenous TILT-123, but not after intratumoral TILT-123. Transcriptional differences were seen in tumors after intravenous therapy and intratumoral therapy, with patients benefitting therapy showing stronger downregulation of immune activation at all time points.
conclusionsTILT-123 therapy induced accumulation of effector lymphocytes in tumors. Peripheral lymphocyte count decrease is a promising biomarker for assessing oncolytic adenovirus therapy response.
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