ArticleJournal for immunotherapy of cancer2021
IL-15 mediated expansion of rare durable memory T cells following adoptive cellular therapy.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Boosting T cell antioxidant capacity: A strategic approach to overcome immunosuppression in solid tumors.Redox biology · 2026Review
- Engineering potent TILs from an immune-excluded tumor: Insights from chondrosarcoma.Molecular therapy. Oncology · 2026Article
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- Engineering resilient CAR T cells for immunosuppressive environment.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Targeted Drug Nanodelivery and Immunotherapy for Combating Tumor Resistance.Combinatorial chemistry & high throughput screening · 2025Review
- Lung cancer organoid-based drug evaluation models and new drug development application trends.Translational lung cancer research · 2024Review
- B7-H3 is widely expressed in soft tissue sarcomas.BMC cancer · 2024Article
- Reprogramming T cell differentiation and exhaustion in CAR-T cell therapy.Journal of hematology & oncology · 2023Review
- Memory T Cells in the Immunoprevention of Cancer: A Switch from Therapeutic to Prophylactic Approaches.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Trial watch: chemotherapy-induced immunogenic cell death in oncology.Oncoimmunology · 2023Review
- B7-H3 Specific CAR T Cells for the Naturally Occurring, Spontaneous Canine Sarcoma Model.Molecular cancer therapeutics · 2022Article
- Exploring the landscape of immunotherapy approaches in sarcomas.Frontiers in oncology · 2022Review
- Interleukin-15 and chemokine ligand 19 enhance cytotoxic effects of chimeric antigen receptor T cells using zebrafish xenograft model of gastric cancer.Frontiers in immunology · 2022Article
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Authors and funding
22 authors at 9 institutions in 2 countries.
Funding
Abstract
backgroundSynovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are ideal solid tumors for the development of adoptive cellular therapy (ACT) targeting NY-ESO-1, as a high frequency of tumors homogeneously express this cancer-testes antigen. Data from early phase clinical trials have shown antitumor activity after the adoptive transfer of NY-ESO-1-specific T cells. In these studies, persistence of NY-ESO-1 specific T cells is highly correlated with response to ACT, but patients often continue to have detectable transferred cells in their peripheral blood following progression.
methodWe performed a phase I clinical trial evaluating the safety of NY-ESO-1-specific endogenous T cells (ETC) following cyclophosphamide conditioning. Peripheral blood mononuclear cells (PBMCs) from treated patients were evaluated by flow cytometry and gene expression analysis as well as through ex vivo culture assays with and without IL-15.
resultsFour patients were treated in a cohort using ETC targeting NY-ESO-1 following cyclophosphamide conditioning. Treatment was well tolerated without significant toxicity, but all patients ultimately had disease progression. In two of four patients, we obtained post-treatment tumor tissue and in both, NY-ESO-1 antigen was retained despite clear detectable persisting NY-ESO-1-specific T cells in the peripheral blood. Despite a memory phenotype, these persisting cells lacked markers of proliferation or activation. However, in ex vivo culture assays, they could be induced to proliferate and kill tumor using IL-15. These results were also seen in PBMCs from two patients who received gene-engineered T-cell receptor-based products at other centers.
conclusionsETC targeting NY-ESO-1 with single-agent cyclophosphamide alone conditioning was well tolerated in patients with SS and those with MRCL. IL-15 can induce proliferation and activity in persisting NY-ESO-1-specific T cells even in patients with disease progression following ACT. These results support future work evaluating whether IL-15 could be incorporated into ACT trials post-infusion or at the time of progression.
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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.