ArticleFrontiers in immunology2023
Development of a Syrian hamster anti-PD-L1 monoclonal antibody enables oncolytic adenoviral immunotherapy modelling in an immunocompetent virus replication permissive setting.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 11 citations in OpenAlex.
- Article
- Propranolol enhances the oncolytic effect of newcastle disease virus on canine mammary tumor cell by modulating the IFN-I-mediated JAK-STAT signaling pathway.The veterinary quarterly · 2026Article
- SNX1 inhibits human ovarian cancer progression via regulation of the cell cycle, apoptosis and migration.Molecular & cellular oncology · 2026Article
- The oncolytic adenovirus TILT-123 with pembrolizumab in platinum resistant or refractory ovarian cancer: the phase 1a PROTA trial.Nature communications · 2025Article
- Synergy of oncolytic adenovirus and immune checkpoint inhibitors: transforming cancer immunotherapy paradigms.Frontiers in immunology · 2025Review
- Oncolytic viruses and antibodies: are they more successful when delivered separately or when engineered as a single agent?Journal for immunotherapy of cancer · 2023Review
- An oncolytic adenovirus coding for a variant interleukin 2 cytokine improves response to chemotherapy through enhancement of effector lymphocyte cytotoxicity, fibroblast compartment modulation and mitotic slippage.Frontiers in immunology · 2023Article
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27 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer, but preclinical testing of hypotheses such as combination therapies has been complicated, in part due to species incompatibility issues. For example, one of few known permissive animal models for oncolytic adenoviruses is the Syrian hamster, for which an ICI, mainly an anti-PD-L1 monoclonal antibody (mAb) was not previously available. In this study, we developed an anti-Syrian hamster PD-L1 mAb to enable the evaluation of safety and efficacy, when combining anti-PD-L1 with an oncolytic adenovirus encoding tumour necrosis factor alpha (TNFα) and interleukin-2 (IL-2) (Ad5/3-E2F-D24-hTNFα-IRES-hIL-2 or TILT-123). Methods: Recombinant Syrian hamster PD-L1 was expressed and mice immunized for mAb formation using hybridoma technology. Clonal selection through binding and functional studies in vitro, in silico and in vivo identified anti-PD-L1 clone 11B12-1 as the primary mAb candidate for immunotherapy modelling. The oncolytic virus (OV) and ICI combination approach was then evaluated using 11B12-1 and TILT-123 in a Syrian hamster model of pancreatic ductal adenocarcinoma (PDAC). Results: Supernatants from hybridoma parent subclone 11B12B4 provided the highest positive PD-L1 signal, on Syrian hamster PBMCs and three cancer cell lines (HT100, HapT1 and HCPC1). In vitro co-cultures revealed superior immune modulated profiles of cell line matched HT100 tumour infiltrating lymphocytes when using subclones of 7G2, 11B12 and 12F1. Epitope binning and epitope prediction using AlphaFold2 and ColabFold revealed two distinct functional epitopes for clone 11B12-1 and 12F1-1. Treatment of Syrian hamsters bearing HapT1 tumours, with 11B12-1 induced significantly better (p<0.05) tumour growth control than isotype control by day 12. 12F1-1 did not induce significant tumour growth control. The combination of 11B12-1 with oncolytic adenovirus TILT-123 improved tumour growth control further, when compared to monotherapy (p<0.05) by day 26. Conclusions: Novel Syrian hamster anti-PD-L1 clone 11B12-1 induces tumour growth control in a hamster model of PDAC. Combining 11B12-1 with oncolytic adenovirus TILT-123 improves tumour growth control further and demonstrates good safety and toxicity profiles.
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