ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Tumor-infiltrating lymphocytes genetically engineered with an inducible gene encoding interleukin-12 for the immunotherapy of metastatic melanoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01236573 (Phase I/II Study of Metastatic Melanoma Using Lymphodepleting Conditioning Followed by Infusion of Tumor Infiltrating Lymphocytes Genetically Engineered to Express IL-12), which is not on this map. Cited by 274 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Phase I/II Study of Metastatic Melanoma Using Lymphodepleting Conditioning Followed by Infusion of Tumor Infiltrating Lymphocytes Genetically Engineered to Express IL-12
Who cites it
274 citing papers in PubMed, 1 synthesis or guideline pooled it, 440 citations in OpenAlex.
- The role of chemokines and interleukins in acute lymphoblastic leukemia: a systematic review.Journal of applied biomedicine · 2024Pooled it
- Extracellular matrix-targeted TNC-scFv armoring enhances CAR T cell persistence and antitumor activity in solid tumors.Science advances · 2026Article
- Epigenetic insights and innovations for overcoming barriers in CAR-T cell therapy for cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- The evolving role of cytokines for CAR-T cell manufacturing and beyond.Nature biomedical engineering · 2026Review
- Armored Chimeric Antigen Receptor T-cell Therapy Targets Antigen-Heterogeneous Glioma.Cancer research · 2026Article
- Progress in the development of cytokine armoured CAR T cells.Nature reviews. Immunology · 2026Review
- Bi-functional anti-LAG-3-IL-2c enhances immune checkpoint inhibitor and CAR T-cell therapy for cancer.iScience · 2026Article
- Potent Cytotoxic Tumor-Infiltrating Lymphocytes Can Be Generated from Immune-Excluded Chondrosarcomas Using Regulatable Membrane-Bound IL15.Cancer immunology research · 2026Article
- The genome takes the wheel: CAR T with built-in circuits.Immuno-oncology technology · 2026Article
- Preclinical evaluation of rBCG-h12: an engineered Bacillus Calmette-Guérin with an enhanced activity against bladder and pancreatic cancers.Cancer immunology, immunotherapy : CII · 2026Article
- Collagen-binding IL-12-armoured STEAP1 CAR-T cells reduce toxicity and treat prostate cancer in mouse models.Nature biomedical engineering · 2026Article
- Solid tumour CAR-T cells engineered with fusion proteins targeting PD-L1 for localized IL-12 delivery.Nature biomedical engineering · 2026Article
- IL-12-secreting CAR-T cells reprogram the tumor microenvironment and improve efficacy against heterogeneous models of glioblastoma.Journal for immunotherapy of cancer · 2026Article
- From Immunobiology to Clinical Application: Tumor-Infiltrating Lymphocytes in Melanoma.Journal of personalized medicine · 2026Review
- The opportunities and barriers for developing tumour-infiltrating lymphocyte therapy for patients with advanced genitourinary cancers.Nature reviews. Urology · 2026Review
- Density of tertiary lymphoid structures predict clinical outcome in hepatoblastoma.Pediatric research · 2026Article
- Therapeutic application of IL-12 for cancer therapy.Translational cancer research · 2026Review
- Regulatory T cell therapies: biological foundations, engineering strategies, and clinical translation.Frontiers in immunology · 2026Review
- CAR-T Cell Therapy in Glioblastoma: Overcoming Immunological Barriers and Advancing Clinical Translation.Cancer management and research · 2026Review
- Non-canonical and induced neoantigens as emerging sources of cancer-specific immunotherapy targets.Frontiers in immunology · 2026Review
214 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
purposeInfusion of interleukin-12 (IL12) can mediate antitumor immunity in animal models, yet its systemic administration to patients with cancer results in minimal efficacy and severe toxicity. Here, we evaluated the antitumor activity of adoptively transferred human tumor-infiltrating lymphocytes (TILs) genetically engineered to secrete single-chain IL12 selectively at the tumor site. EXPERIMENTAL
designThirty-three patients with metastatic melanoma were treated in a cell dose-escalation trial of autologous TILs transduced with a gene encoding a single-chain IL12 driven by a nuclear factor of the activated T cells promoter (NFAT.IL12). No IL2 was administered.
resultsThe administration of 0.001 to 0.1 × 10(9) NFAT.IL12-transduced TILs to 17 patients resulted in a single, objective response (5.9%). However, at doses between 0.3 and 3 × 10(9) cells, 10 of 16 patients (63%) exhibited objective clinical responses. The responses tended to be short, and the administered IL12-producing cells rarely persisted at 1 month. Increasing cell doses were associated with high serum levels of IL12 and IFNγ as well as clinical toxicities, including liver dysfunction, high fevers, and sporadic life-threatening hemodynamic instability.
conclusionsIn this first-in-man trial, administration of TILs transduced with an inducible IL12 gene mediated tumor responses in the absence of IL2 administration using cell doses 10- to 100-fold lower than conventional TILs. However, due to toxicities, likely attributable to the secreted IL12, further refinement will be necessary before this approach can be safely used in the treatment of cancer patients.
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Registered trials
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.