ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
Short-Term Local Expression of a PD-L1 Blocking Antibody from a Self-Replicating RNA Vector Induces Potent Antitumor Responses.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 40 citations in OpenAlex.
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- Alphaviral backbone of self-amplifying RNA enhances protein expression and immunogenicity against SARS-CoV-2 antigen.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Targeting PD-1Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Macrophage Transcriptomic Alterations Driven by Alphavirus-Based Cancer Immunotherapy Vectors.Journal of immunology research · 2025Article
- Cellular mechanisms of combining innate immunity activation with PD-1/PD-L1 blockade in treatment of colorectal cancer.Molecular cancer · 2024Review
- mRNA vaccine development and applications: A special focus on tumors (Review).International journal of oncology · 2024Review
- Article
- Oleuropein-driven reprogramming of the myeloid cell compartment to sensitise tumours to PD-1/PD-L1 blockade strategies.British journal of cancer · 2024Article
- Recent progress in combination therapy of oncolytic vaccinia virus.Frontiers in immunology · 2024Review
- Channeling the Natural Properties of Sindbis Alphavirus for Targeted Tumor Therapy.International journal of molecular sciences · 2023Review
- Preclinical and clinical trials of oncolytic vaccinia virus in cancer immunotherapy: a comprehensive review.Cancer biology & medicine · 2023Review
- Viral Replicon Systems and Their Biosafety Aspects.Applied biosafety : journal of the American Biological Safety Association · 2023Review
- Review
- Leading Edge: Intratumor Delivery of Monoclonal Antibodies for the Treatment of Solid Tumors.International journal of molecular sciences · 2023Review
- Systemic Checkpoint Blockade by PD-L1 Single-Chain Antibody Confers Potent Antitumor Immunity and Long-term Survival.Molecular cancer therapeutics · 2022Article
- CPEB3 suppresses gastric cancer progression by inhibiting ADAR1-mediated RNA editing via localizing ADAR1 mRNA to P bodies.Oncogene · 2022Article
- Intratumoral electroporation of a self-amplifying RNA expressing IL-12 induces antitumor effects in mouse models of cancer.Molecular therapy. Nucleic acids · 2022Article
- Recombinant Viral Vectors for Therapeutic Programming of Tumour Microenvironment: Advantages and Limitations.Biomedicines · 2022Review
- Idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma.Scientific reports · 2021Article
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune checkpoint blockade has shown anti-cancer efficacy, but requires systemic administration of monoclonal antibodies (mAbs), often leading to adverse effects. To avoid toxicity, mAbs could be expressed locally in tumors. We developed adeno-associated virus (AAV) and Semliki Forest virus (SFV) vectors expressing anti-programmed death ligand 1 (aPDL1) mAb. When injected intratumorally in MC38 tumors, both viral vectors led to similar local mAb expression at 24 h, diminishing quickly in SFV-aPDL1-treated tumors. However, SFV-aPDL1 induced >40% complete regressions and was superior to AAV-aPDL1, as well as to aPDL1 mAb given systemically or locally. SFV-aPDL1 induced abscopal effects and was also efficacious against B16-ovalbumin (OVA). The higher SFV-aPDL1 antitumor activity could be related to local upregulation of interferon-stimulated genes because of SFV RNA replication. This was confirmed by combining local SFV-LacZ administration and systemic aPDL1 mAb, which provided higher antitumor effects than each separated agent. SFV-aPDL1 promoted tumor-specific CD8 T cells infiltration in both tumor models. In MC38, SFV-aPDL1 upregulated co-stimulatory markers (CD137/OX40) in tumor CD8 T cells, and its combination with anti-CD137 mAb showed more pronounced antitumor effects than each single agent. These results indicate that local transient expression of immunomodulatory mAbs using non-propagative RNA vectors inducing type I interferon (IFN-I) responses represents a potent and safe approach for cancer treatment.
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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.