ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Mesenchymal stromal cell delivery of oncolytic immunotherapy improves CAR-T cell antitumor activity.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.
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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.
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- Next-generation oncolytic virotherapy for lung cancer: bridging innovative vector engineering with clinical immunotherapy.Translational lung cancer research · 2026Review
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- Th17-driven CD8Cell death & disease · 2026Article
- Beyond autologousMolecular therapy. Oncology · 2026Review
- Cytokine-Engineered Chimeric Antigen Receptor-T Cell Therapy: How to Balance the Efficacy and Toxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.Precision clinical medicine · 2026Review
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- CAR T Cell Therapy in Lung Cancer: Overcoming Tumor Microenvironment-Mediated Barriers.International journal of biological sciences · 2026Review
- CAR-T therapy: Advances in respiratory diseases.Chinese medical journal pulmonary and critical care medicine · 2025Review
- Mesenchymal Stem Cell-Mediated Targeted Drug Delivery Systems for Hepatocellular Carcinoma: Current Advances and Future Directions.Bioengineering (Basel, Switzerland) · 2025Review
- Recent advances in CAR-MSCs: the new engine of cellular immunotherapy evolution.Journal of hematology & oncology · 2025Review
- The Role of Mesenchymal Stem Cells in Drug Resistance in Lung Neoplasms.Journal of cancer prevention · 2025Review
- Improving CAR-T cell function through a targeted cytokine delivery system utilizing car target-modified extracellular vesicles.Experimental hematology & oncology · 2025Article
- Review
- Antitumor Efficacy of Interleukin 12-Transfected Mesenchymal Stem Cells in B16-F10 Mouse Melanoma Tumor Model.Pharmaceutics · 2025Article
- Engineered mesenchymal stem/stromal cells against cancer.Cell death & disease · 2025Review
- Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method.Pharmaceuticals (Basel, Switzerland) · 2025Review
- From spheroids to organoids: next-generation models for CAR-T cell therapy research in solid tumors.Frontiers in immunology · 2025Review
- Interleukin-12 Delivery Strategies and Advances in Tumor Immunotherapy.Current issues in molecular biology · 2024Review
- Mesenchymal stromal cells protect combined oncolytic and helper-dependent adenoviruses from humoral immunity.Molecular therapy. Methods & clinical development · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The immunosuppressive tumor microenvironment (TME) is a formidable barrier to the success of adoptive cell therapies for solid tumors. Oncolytic immunotherapy with engineered adenoviruses (OAd) may disrupt the TME by infecting tumor cells, as well as surrounding stroma, to improve the functionality of tumor-directed chimeric antigen receptor (CAR)-T cells, yet efficient delivery of OAds to solid tumors has been challenging. Here we describe how mesenchymal stromal cells (MSCs) can be used to systemically deliver a binary vector containing an OAd together with a helper-dependent Ad (HDAd; combinatorial Ad vector [CAd]) that expresses interleukin-12 (IL-12) and checkpoint PD-L1 (programmed death-ligand 1) blocker. CAd-infected MSCs deliver and produce functional virus to infect and lyse lung tumor cells while stimulating CAR-T cell anti-tumor activity by release of IL-12 and PD-L1 blocker. The combination of this approach with administration of HER.2-specific CAR-T cells eliminates 3D tumor spheroids in vitro and suppresses tumor growth in two orthotopic lung cancer models in vivo. Treatment with CAd MSCs increases the overall numbers of human T cells in vivo compared to CAR-T cell only treatment and enhances their polyfunctional cytokine secretion. These studies combine the predictable targeting of CAR-T cells with the advantages of cancer cell lysis and TME disruption by systemic MSC delivery of oncolytic virotherapy: incorporation of immunostimulation by cytokine and checkpoint inhibitor production through the HDAd further enhances anti-tumor activity.
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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.