ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026
Dyslipidemia-associated natural IgM improves oncolytic virus TILT-123 efficacy through antibody-dependent enhancement in solid tumors.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 1 paper.
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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 Melanoma Patients Receiving Adoptive Cell Therapy With Tumor Infiltrating Lymphocytes
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
A Two-part, Phase I/Ib, Open-Label, Dose-escalation Trial of Tumor Necrosis Factor Alpha and Interleukin-2 Coding Oncolytic Adenovirus (TILT-123) in Combination With Pembrolizumab (Phase I Part) and Pembrolizumab and Pegylated Liposomal Doxorubicin (Phase Ib Part) in Patients With Platinum Resistant or Refractory Ovarian Cancer
Who cites it
1 citing paper in PubMed.
- Fire in an Icy Desert: Oncolytic Virotherapy for Pancreatic Adenocarcinoma.Pharmaceutics · 2026Review
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Authors and funding
34 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The oncolytic adenovirus TILT-123 (Ad5/3-E2F-d24-hTNFA-IRES-hIL2, igrelimogene litadenorepvec) has demonstrated favorable safety profiles in phase 1 clinical trials in patients with advanced solid tumors (these trials were registered at ClinicalTrials.gov: NCT04695327, NCT05271318, and NCT04217473). In this study, we analyzed the serum proteome of patients treated with TILT-123 monotherapy using mass spectrometry, focusing on samples collected during the initial intravenous administration phase. Functional and correlative analyses revealed that IGLV8-61-encoded natural immunoglobulin M (IgM) was associated with reduced neutralizing activity and improved clinical outcomes, as assessed by positron emission tomography imaging and overall survival. Single-cell B cell receptor sequencing enabled profiling of the circulating antibody repertoire and detection of IGLV8-61-expressing clones. Recombinant expression of antibody sequences from a responding patient with a history of hyperlipidemia yielded three pentameric natural IgMs capable of binding both TILT-123 and anionic modified low-density lipoprotein. Further characterization revealed that the IgMs significantly enhanced transduction and promoted cell killing in vitro across multiple cell lines. Blocking studies demonstrated transduction was influenced by Fc receptors pIgR and FcμR. Cross-trial comparisons indicated dyslipidemia as a common feature among responders. Collectively these findings show that dyslipidemia -associated natural IgM enhances the therapeutic efficacy of TILT-123, via antibody-dependent enhancement. These findings may have broader implications for other oncolytic viruses, an emerging class of tumor immunotherapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.