ArticleNature communications2023
Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed.
- Multifaceted roles of chemokines in gastric cancer: From tumor microenvironment modulation to therapeutic targeting (Review).Oncology letters · 2026Review
- Extracellular matrix-targeted TNC-scFv armoring enhances CAR T cell persistence and antitumor activity in solid tumors.Science advances · 2026Article
- Armored Chimeric Antigen Receptor T-cell Therapy Targets Antigen-Heterogeneous Glioma.Cancer research · 2026Article
- Mechanisms, optimization strategies, and salvage options for CAR-T cell therapy.Biomarker research · 2026Review
- CAR-T and TIL therapies in solid tumors: barriers, clinical lessons, and convergent solutions.Cancer cell international · 2026Review
- Advances in cancer immunotherapy: adoptive cell therapy and immune cell engagers in solid tumours.British journal of cancer · 2026Review
- Novel approaches to modulate CAR-T cell function by targeting the tumor microenvironment in ovarian cancer.Journal of ovarian research · 2026Review
- IL-12-engineered human PSMA-CAR T cells for the treatment of advanced prostate cancer.Molecular therapy. Advances · 2026Article
- NCOR2 represses MHC class I molecule expression to drive metastatic progression of breast cancer.Nature communications · 2026Article
- Engineering CAR-Vδ2 T cells to boost persistence and anti-tumor function.bioRxiv : the preprint server for biology · 2026Article
- Arming oncolytic herpes simplex virus with CXCL-11, IL-12 and a single-chain antibody against PD-1 to enhance CAR-T cell therapy in pancreatic ductal adenocarcinoma.Cell death & disease · 2026Article
- In vivo CAR-T therapy: from molecular design to precision delivery.Journal of nanobiotechnology · 2026Review
- Solid tumour CAR-T cells engineered with fusion proteins targeting PD-L1 for localized IL-12 delivery.Nature biomedical engineering · 2026Article
- Natural and Engineered Cytokines as Cancer Therapeutics.Annual review of cancer biology · 2026Article
- Collagen-binding IL-12-armoured STEAP1 CAR-T cells reduce toxicity and treat prostate cancer in mouse models.Nature biomedical engineering · 2026Article
- A low-toxicity circular single-stranded DNA platform for safe and potent IL-12 immunotherapy against hepatocellular carcinoma.Journal of nanobiotechnology · 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
- CAR-T cell exhaustion in B cell lymphoma: Current status, mechanisms, and potential solutions.Molecular therapy. Oncology · 2026Review
- <p>Converting 'cold' to 'hot' hepatocellular carcinoma for improved immunotherapy (Review)</p>.Molecular medicine reports · 2026Review
- T cells assemble lentivirus to solve local delivery of stable gene therapy.Scientific reports · 2026Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors.
Funding
Abstract
Chimeric antigen receptor (CAR) T cell therapeutic responses are hampered by limited T cell trafficking, persistence, and durable anti-tumor activity in solid tumors. However, these challenges can be largely overcome by relatively unconstrained synthetic engineering strategies. Here, we describe CAR T cells targeting tumor-associated glycoprotein-72 (TAG72), utilizing the CD28 transmembrane domain upstream of the 4-1BB co-stimulatory domain as a driver of potent anti-tumor activity and IFNγ secretion. CAR T cell-mediated IFNγ production facilitated by IL-12 signaling is required for tumor cell killing, which is recapitulated by engineering an optimized membrane-bound IL-12 (mbIL12) molecule in CAR T cells. These T cells show improved antigen-dependent T cell proliferation and recursive tumor cell killing in vitro, with robust in vivo efficacy in human ovarian cancer xenograft models. Locoregional administration of mbIL12-engineered CAR T cells promotes durable anti-tumor responses against both regional and systemic disease in mice. Safety and efficacy of mbIL12-engineered CAR T cells is demonstrated using an immunocompetent mouse model, with beneficial effects on the immunosuppressive tumor microenvironment. Collectively, our study features a clinically-applicable strategy to improve the efficacy of locoregionally-delivered CAR T cells engineered with antigen-dependent immune-modulating cytokines in targeting regional and systemic disease.
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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.