ArticleJournal for immunotherapy of cancer2024
Tethered IL15-IL15Rα augments antitumor activity of CD19 CAR-T cells but displays long-term toxicity in an immunocompetent lymphoma mouse model.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Constitutive RLI Armoring Enhances CAR-NK Cell Effector Functions but Causes Lethal Toxicity In Vivo.International journal of molecular sciences · 2026Article
- Redesigning CAR therapy to tackle immune effector cell-associated hematotoxicity.Annals of hematology · 2026Review
- IL-15 overexpression promotes memory program and anti-tumor activity of CD64 CAR T cells in a preclinical AML model.Communications biology · 2026Article
- The impact of the large B-cell lymphoma tumor microenvironment on efficacy of CD19-directed CAR-T immunotherapy.Frontiers in immunology · 2026Review
- The resilient subset: cancer stem cells at the core of immunotherapy resistance.Immunotherapy advances · 2026Review
- A novel immunocytokine promotes T cell- and cytokine-induced killer cell-mediated antitumor immunity via a non-MHC-restricted mechanism in glioblastoma.Journal of translational medicine · 2025Article
- Leveraging liquid biopsy to uncover resistance mechanisms and guide personalized immunotherapy.Translational oncology · 2025Review
- Review
- Novel mRNA-Engineered Fully Human CAR-T Cells Targeting AXL in Solid Tumors.Biomedicines · 2025Article
- Phosphatidylserine as a tumor target for CAR-T cell therapy.Journal for immunotherapy of cancer · 2025Article
- IL-15: from discovery to FDA approval.Journal of hematology & oncology · 2025Article
- Current strategies for armoring chimeric antigen receptor T-cells to overcome barriers of the solid tumor microenvironment.Frontiers in immunology · 2025Review
- IL-7 armed binary CAR T cell strategy to augment potency against solid tumors.Frontiers in immunology · 2025Article
- Logic-gated and contextual control of immunotherapy for solid tumors: contrasting multi-specific T cell engagers and CAR-T cell therapies.Frontiers in immunology · 2024Review
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Authors and funding
14 authors.
Funding
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Abstract
backgroundAdoptive cell therapy using genetically modified T cells to express chimeric antigen receptors (CAR-T) has shown encouraging results, particularly in certain blood cancers. Nevertheless, over 40% of B cell malignancy patients experience a relapse after CAR-T therapy, likely due to inadequate persistence of the modified T cells in the body. IL15, known for its pro-survival and proliferative properties, has been suggested for incorporation into the fourth generation of CAR-T cells to enhance their persistence. However, the potential systemic toxicity associated with this cytokine warrants further evaluation.
methodsWe analyzed the persistence, antitumor efficacy and potential toxicity of anti-mouse CD19 CAR-T cells which express a membrane-bound IL15-IL15Rα chimeric protein (CD19/mbIL15q CAR-T), in BALB/c mice challenged with A20 tumor cells as well as in NSG mice.
resultsConventional CD19 CAR-T cells showed low persistence and poor efficacy in BALB/c mice treated with mild lymphodepletion regimens (total body irradiation (TBI) of 1 Gy). CD19/mbIL15q CAR-T exhibits prolonged persistence and enhanced in vivo efficacy, effectively eliminating established A20 B cell lymphoma. However, this CD19/mbIL15q CAR-T displays important long-term toxicities, with marked splenomegaly, weight loss, transaminase elevations, and significant inflammatory findings in some tissues. Mice survival is highly compromised after CD19/mbIL15q CAR-T cell transfer, particularly if a high TBI regimen is applied before CAR-T cell transfer.
conclusionTethered IL15-IL15Rα augments the antitumor activity of CD19 CAR-T cells but displays long-term toxicity in immunocompetent mice. Inducible systems to regulate IL15-IL15Rα expression could be considered to control this toxicity.
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