ArticleGastroenterology2022
Off-the-Shelf Prostate Stem Cell Antigen-Directed Chimeric Antigen Receptor Natural Killer Cell Therapy to Treat Pancreatic Cancer.
Article in Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed.
- Dynamic transcriptional immune landscape in response to NK-cell therapy combined with gemcitabine plus S-1 in advanced pancreatic cancer: a phase 1b/2 trial.Signal transduction and targeted therapy · 2025Trial
- Review
- CD28-ICOS costimulation enhances the therapeutic efficacy of L1CAM-targeted CAR-T cells against ovarian and gastric cancers.Journal for immunotherapy of cancer · 2026Article
- Barriers and Blueprints: Next-Generation Engineering Strategies for CAR-T Cell Therapy in Gastrointestinal Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Migration of immune cells in tumors and inflammation: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- The Oncogenic Role of Prostate Stem Cell Antigen (PSCA) in Colorectal Cancer: Implications for Targeted Therapy.Current issues in molecular biology · 2026Article
- Systemic immunosuppression limits NK cell therapy efficacy in pancreatic cancer.Molecular cancer · 2026Article
- Optimizing In Vivo CAR T-cell Engineering for Cancer Immunotherapy.Cancer research · 2026Review
- Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.Precision clinical medicine · 2026Review
- Human pluripotent stem cell-derived innate and adaptive immune cells for cancer immunotherapy.Cell stem cell · 2026Review
- Hypoxic-immune axis orchestrates metastatic dissemination via HIF isoform imbalance in pancreatic neuroendocrine tumors.iScience · 2026Article
- Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.Research (Washington, D.C.) · 2026Article
- Emerging Chimeric Antigen Receptor-Immune Cell Therapy for Pancreatic Cancer: Mechanisms, Clinical Advances, and Future Perspectives.Oncology research · 2026Review
- Overcoming multidimensional immunotherapy resistance in PDAC: from microenvironment to clinic.Frontiers in immunology · 2026Review
- Anti-MSLN chimeric antigen receptor-like NK cell therapy with tumor-penetrating capacity (uCAR-like NK) for solid tumors.Signal transduction and targeted therapy · 2025Article
- Antibody-Mediated In Vitro Activation and Expansion of Blood Donor-Derived Natural Killer Cells with Transient Anti-Tumor Efficacy.Biomedicines · 2025Article
- Potency of human hematopoietic cells from a novel CD34+ isolation technique.Stem cells translational medicine · 2025Article
- Multiplexed iPSC platform for advanced NK cell immunotherapies.Cell reports. Medicine · 2025Review
- Directly reprogrammed NK cells driven by BCL11B depletion enhance targeted immunotherapy against pancreatic ductal adenocarcinoma.Journal of hematology & oncology · 2025Article
- Site-specific genome engineering of primary human natural killer cells for programmable anti-tumor function.bioRxiv : the preprint server for biology · 2025Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors.
Funding
Abstract
BACKGROUND &
aimsPancreatic cancer (PC) is the third leading cause of cancer-related death with a 5-year survival rate of approximately 10%. It typically presents as a late-stage incurable cancer and chemotherapy provides modest benefit. Here, we demonstrate the feasibility, safety, and potency of a novel human natural killer (NK) cell-based immunotherapy to treat PC.
methodsThe expression of prostate stem cell antigen (PSCA) was evaluated in primary PC at messenger RNA and protein levels. The processes of retroviral transduction, expansion, activation, and cryopreservation of primary human NK cells obtained from umbilical cord blood were optimized, allowing us to develop frozen, off-the-shelf, allogeneic PSCA chimeric antigen receptor (CAR) NK cells. The safety and efficacy of PSCA CAR NK cells also expressing soluble (s) interleukin 15 (PSCA CAR_s15 NK cells) were evaluated in vitro and in vivo.
resultsPSCA was elevated in primary human PC compared with the adjacent or other normal tissues. PSCA CAR_s15 NK cells displayed significant tumor-suppressive effects against PSCA(+) PC in vitro before and after 1 cycle of freeze-thaw. The viability of frozen PSCA CAR_s15 NK cells persisted more than 90 days in vivo after their last infusion and significantly prolonged the survival of mice engrafted with human PC.
conclusionsPSCA CAR_s15 NK cells showed therapeutic efficacy in human metastatic PC models without signs of systematic toxicity, providing a strong rationale to support clinical development.
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