ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
IL-2-independent expansion, persistence, and antitumor activity in TIL expressing regulatable membrane-bound IL-15.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Review
- The evolution of cellular-based immunotherapy in the treatment of gastric cancer: an overview of clinical trials.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Engineering potent TILs from an immune-excluded tumor: Insights from chondrosarcoma.Molecular therapy. Oncology · 2026Article
- Cellular immunotherapy in melanoma: the next frontier in cancer treatment.Journal of experimental & clinical cancer research : CR · 2026Review
- Potent Cytotoxic Tumor-Infiltrating Lymphocytes Can Be Generated from Immune-Excluded Chondrosarcomas Using Regulatable Membrane-Bound IL15.Cancer immunology research · 2026Article
- Constitutive RLI Armoring Enhances CAR-NK Cell Effector Functions but Causes Lethal Toxicity In Vivo.International journal of molecular sciences · 2026Article
- From Immunobiology to Clinical Application: Tumor-Infiltrating Lymphocytes in Melanoma.Journal of personalized medicine · 2026Review
- Multiple autologous tumor-infiltrating lymphocyte (LM103 infusion) therapy combined with immune checkpoint inhibitor induces repeated tumor regression in a patient with aggressive mucosal melanoma: a case report and literature review.Frontiers in oncology · 2026Article
- CRISPR-screen informed engineered T cell therapies.Frontiers in immunology · 2026Review
- The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee.Journal for immunotherapy of cancer · 2025Review
- Targeting tumor-draining lymph node to overcome resistance to cancer immunotherapy: an update.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Tumour-infiltrating lymphocyte therapy landscape: prospects and challenges.BMJ oncology · 2025Review
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Authors and funding
20 authors.
Funding
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Abstract
Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) has demonstrated great potential for patients with treatment-refractory metastatic melanoma. However, the need for interleukin-2 (IL-2) co-administration during TIL cell therapy limits patient eligibility and restricts treatment to intensive care units due to the risk of severe side effects. Instead, engineering TIL with membrane-bound interleukin-15 (mbIL15) has the potential to promote TIL expansion, antitumor activity, and persistence of CD8+ T cells, without the use of IL-2. cytoTIL15 cells express mbIL15 fused to a drug-responsive domain (DRD) that is regulated by the Food and Drug Administration-approved small-molecule drug acetazolamide (ACZ). As such, cytoTIL15 cells are manufactured with ACZ instead of IL-2, in the presence of engineered feeder cells. The cytoTIL15 cell product exhibits ACZ dose-dependent expansion and persistence in vitro and in vivo and potent tumor-killing activity in human melanoma models in the absence of IL-2. In patient-derived xenograft (PDX) tumors, spatial profiling revealed infiltrating cytoTIL15 cells to be highly cytotoxic and less exhausted than non-engineered TIL. This novel platform creates a powerful, IL-2-free TIL cell therapy with a potentially improved tolerability and safety profile, while allowing individualized pharmacologic regulation of the TIL product.
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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.