ArticleJournal for immunotherapy of cancer2019
Targeting the tumor stroma with an oncolytic adenovirus secreting a fibroblast activation protein-targeted bispecific T-cell engager.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 149 citations in OpenAlex.
- Targeting cancer-associated fibroblasts: therapeutic strategies, translational challenges, and future perspectives.Journal of hematology & oncology · 2026Review
- Next-generation oncolytic virotherapy for lung cancer: bridging innovative vector engineering with clinical immunotherapy.Translational lung cancer research · 2026Review
- Emergence of a mixed CAF population by FAP-CD3 T-cell engager limits therapeutic efficacy.Journal for immunotherapy of cancer · 2026Article
- Cracking the shield: oncolytic viruses versus the tumor-immune fortress.Cancer cell international · 2026Review
- Review
- Targeted therapies in pediatric oncology: A start.Molecular therapy. Oncology · 2026Review
- Oncolytic adenoviruses encoding bispecific T cell engagers or a novel trispecific T cell engager for dual-targeting of c-MET and EGFR.Molecular therapy. Oncology · 2026Article
- Oncolytic viruses: advanced strategies in cancer therapy.Signal transduction and targeted therapy · 2026Review
- Immune cell engagers in lung cancer.Frontiers in immunology · 2026Review
- Cancer-associated fibroblasts: central players in cancer hallmarks and therapeutic resistance.Cell communication and signaling : CCS · 2025Review
- Cancer-associated fibroblasts at the crossroads of tumor progression and therapy resistance: from heterogeneity to precision reprogramming.Journal of the Egyptian National Cancer Institute · 2025Review
- Impact of pancreatic proenzymes on pancreatic ductal adenocarcinoma associated fibroblasts.Scientific reports · 2025Article
- Bispecific antibodies and nanotechnology: a strategic alliance in cancer immunotherapy.Molecular cancer · 2025Review
- Review
- Resistance to oncolytic virotherapy: Multidimensional mechanisms and therapeutic breakthroughs (Review).International journal of molecular medicine · 2025Review
- Crosstalk between heterogeneous cancer-associated fibroblast subpopulations and the immune system in breast cancer: key players and promising therapeutic targets.Journal of experimental & clinical cancer research : CR · 2025Review
- Cancer-associated fibroblasts in cancer drug resistance and cancer progression: a review.Cell death discovery · 2025Review
- Fibroblasts in immune responses, inflammatory diseases and therapeutic implications.Nature reviews. Rheumatology · 2025Review
- Oncolytic viruses as cancer therapeutics: From mechanistic insights to clinical translation.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects.Journal of advanced research · 2025Review
52 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOncolytic virus (OV)-based therapies have an emerging role in the treatment of solid tumors, involving both direct cell lysis and immunogenic cell death. Nonetheless, tumor-associated stroma limits the efficacy of oncolytic viruses by forming a barrier that blocks efficient viral penetration and spread. The stroma also plays a critical role in progression, immunosuppression and invasiveness of cancer. Fibroblast activation protein-α (FAP) is highly overexpressed in cancer-associated fibroblasts (CAFs), the main cellular component of tumor stroma, and in this study we assessed whether arming oncolytic adenovirus (OAd) with a FAP-targeting Bispecific T-cell Engager (FBiTE) could retarget infiltrated lymphocytes towards CAFs, enhancing viral spread and T cell-mediated cytotoxicity against the tumor stroma to improve therapeutic activity.
methodsThe bispecific T-cell Engager against FAP was constructed using an anti-human CD3 single-chain variable fragment (scFv) linked to an anti-murine and human FAP scFv. This FBiTE was inserted in the oncolytic adenovirus ICOVIR15K under the control of the major late promoter, generating the ICO15K-FBiTE. ICO15K-FBiTE replication and potency were assessed in HT1080 and A549 tumor cell lines. The expression of the FBiTE and the activation and proliferation of T cells that induced along with the T cell-mediated cytotoxicity of CAFs were evaluated by flow cytometry in vitro. In vivo, T-cell biodistribution and antitumor efficacy studies were conducted in NOD/scid/IL2rg
resultsFBiTE expression did not decrease the infectivity and replication potency of the armed virus. FBiTE-mediated binding of CD3
conclusionsCombination of viral oncolysis of cancer cells and FBiTE-mediated cytotoxicity of FAP-expressing CAFs might be an effective strategy to overcome a key limitation of oncolytic virotherapy, encouraging its further clinical development.
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