ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Adenovirus Coding for Interleukin-2 and Tumor Necrosis Factor Alpha Replaces Lymphodepleting Chemotherapy in Adoptive T Cell Therapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 54 citations in OpenAlex.
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- The opportunities and barriers for developing tumour-infiltrating lymphocyte therapy for patients with advanced genitourinary cancers.Nature reviews. Urology · 2026Review
- Recent advances in oncolytic virus combined immunotherapy in tumor treatment.Genes & diseases · 2025Review
- Novel oncolytic adenovirus-based PEPvIII vaccine displays a super antitumor effect in glioma models.Journal for immunotherapy of cancer · 2025Article
- Tumor infiltration therapy: from FDA approval to next-generation approaches.Clinical and experimental medicine · 2025Review
- Safety and efficacy of combined treatment with tumor-infiltrating lymphocytes and oncolytic adenovirus TILT-123 in metastatic melanoma.Cell reports. Medicine · 2025Article
- Advances and prospects in tumor infiltrating lymphocyte therapy.Discover oncology · 2024Review
- An oncolytic adenovirus co-expressing a bi-specific T cell engager and IL-2 for the treatment of ovarian cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Harnessing adenovirus in cancer immunotherapy: evoking cellular immunity and targeting delivery in cell-specific manner.Biomarker research · 2024Review
- The investigation of oncolytic viruses in the field of cancer therapy.Frontiers in oncology · 2024Review
- Viral Vectors Expressing Interleukin 2 for Cancer Immunotherapy.Human gene therapy · 2023Review
- Syrian hamster as an ideal animal model for evaluation of cancer immunotherapy.Frontiers in immunology · 2023Review
- Engineered Oncolytic Adenoviruses: An Emerging Approach for Cancer Therapy.Pathogens (Basel, Switzerland) · 2022Review
- Tumor Infiltrating Lymphocyte (TIL) Therapy for Solid Tumor Treatment: Progressions and Challenges.Cancers · 2022Review
- Oncolytic effect of SARS-CoV-2 in a patient with mycosis fungoides: A case report.Clinical case reports · 2022Article
- Controlling Cell Trafficking: Addressing Failures in CAR T and NK Cell Therapy of Solid Tumours.Cancers · 2022Review
- Role of Adenoviruses in Cancer Therapy.Frontiers in oncology · 2022Review
- Dendritic cells and natural killer cells: The road to a successful oncolytic virotherapy.Frontiers in immunology · 2022Review
- Metabolic reprogramming of terminally exhausted CD8Nature immunology · 2021Article
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9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lymphodepleting preconditioning with high-dose chemotherapy is commonly used to increase the clinical efficacy of adoptive T cell therapy (ACT) strategies, however, with severe toxicity for patients. Conversely, oncolytic adenoviruses are safe and, when engineered to express interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-α), they can achieve antitumor immunomodulatory effects similar to lymphodepletion. Therefore, we compare the safety and efficacy of such adenoviruses with a cyclophosphamide- and fludarabine-containing lymphodepleting regimen in the setting of ACT. Human adenovirus (Ad5/3-E2F-D24-hTNF-α-IRES-hIL-2; TILT-123) replication was studied using a Syrian hamster pancreatic tumor model (HapT1) infused with tumor-infiltrating lymphocytes (TILs). Using the oncolytic virus instead of lymphodepletion resulted in superior efficacy and survival. Immune cells responsive to TNF-α IL-2 were studied using an immunocompetent mouse melanoma model (B16.OVA) infused with ovalbumin-specific T (OT-I) cells. Here, the adenovirus approach improved tumor control together with increased intratumoral Th1 cytokine levels and infiltration of CD8+ T cells and CD86+ dendritic cells. Similar to humans, lymphodepleting preconditioning caused severe cytopenias, systemic inflammation, and damage to vital organs. Toxicity was minimal in adenovirus- and OT-I-treated mice. These findings demonstrate that ACT can be effectively facilitated by cytokine-coding adenovirus without requiring lymphodepletion, a rationale being clinically investigated.
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