ArticleJournal for immunotherapy of cancer2023
An anti-mesothelin targeting antibody drug conjugate induces pyroptosis and ignites antitumor immunity in mouse models of cancer.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Chlamydia psittaci induces GSDME-mediated pyroptosis via the ROS-JNK signaling pathway.Molecular and cellular biochemistry · 2026Article
- A pneumolysin mutant (ΔA146 ply) induces pyroptosis in triple-negative and HER2-positive breast cancer cells via the Caspase-1/GSDME pathway: a potential antibody-drug conjugate payload.Translational cancer research · 2026Article
- A DNA Vaccine Incorporating the MHC Class I Trafficking Domain and PADRE Epitope Enhances Antitumor Immunity in a Murine Pancreatic Cancer Model.International journal of molecular sciences · 2026Article
- Frontiers in Antibody-Drug Conjugates: Mechanisms, Design Innovations, and Clinical Applications in Targeted Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Novel perspectives on MSLN-targeted cancer therapy: from molecular mechanisms to clinical translation.Cancer biology & therapy · 2025Review
- Decoding the role of mesothelin in tumor dynamics and targeted treatment innovations.Molecular biomedicine · 2025Review
- Antibody-drug conjugates in cancer therapy: current landscape, challenges, and future directions.Molecular cancer · 2025Review
- Targeting uPAR with an antibody-drug conjugate suppresses tumor growth and reshapes the immune landscape in pancreatic cancer models.Science advances · 2025Article
- Mesothelin-Mediated Paclitaxel Phase-Shifted Nanodelivery System for Molecular Ultrasound Imaging and Targeted Therapy Potential in Ovarian Cancer.Current drug delivery · 2025Article
- Evaluation of pyroptosis-associated genes in endometrial cancer utilizing a 101-combination machine learning framework and multi-omics data.Frontiers in medicine · 2025Article
- Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication.Molecular cancer · 2024Review
- Research progress on the effect of pyroptosis on the occurrence, development, invasion and metastasis of colorectal cancer.World journal of gastrointestinal oncology · 2024Review
- The gasdermin family: emerging therapeutic targets in diseases.Signal transduction and targeted therapy · 2024Review
- Mesothelin promotes brain metastasis of non-small cell lung cancer by activating MET.Journal of experimental & clinical cancer research : CR · 2024Article
- Gasdermin-mediated pyroptosis confers anticancer immunity.Journal for immunotherapy of cancer · 2024Article
- The multifaceted roles of GSDME-mediated pyroptosis in cancer: therapeutic strategies and persisting obstacles.Cell death & disease · 2023Review
- Antibody drug conjugates: hitting the mark in pancreatic cancer?Journal of experimental & clinical cancer research : CR · 2023Review
- Effect of tumor-associated macrophages on the pyroptosis of breast cancer tumor cells.Cell communication and signaling : CCS · 2023Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEmerging evidence suggests that the mechanism of chemotherapy-induced cell death may influence the antitumor immune response in patients with cancer. Unlike immunologically silent apoptosis, pyroptosis is a lytic and inflammatory form of programmed cell death characterized by pore formation in the cell membrane and release of proinflammatory factors. Gasdermin E (GSDME) has recently gained attention after cleavage of GSDME by certain chemotherapeutics has been shown to elicit pyroptosis. This study investigated the immunomodulatory effects of a mesothelin-targeting antibody drug conjugate (ADC) in mouse models of breast and colon cancer.
methodsThe antitumor effects of the ADC were studied in EMT6 breast cancer and CT26 colon cancer syngeneic mouse models. The immunomodulatory effects of the ADC were assessed by analysis of tumor-infiltrating immune cells using flow cytometry. ADC mechanism of action was evaluated by morphology, biological assays, ADC-mediated cleavage of key effector proteins, and CRISPR/Cas9-mediated knockout (KO). Finally, the antitumor effect of ADC and Fms-like tyrosine kinase-3 ligand (Flt3L) combination therapy was evaluated in tumors expressing GSDME as well as in GSDME-silenced tumors.
resultsThe data demonstrated that the ADC controlled tumor growth and stimulated anticancer immune responses. Investigation of the mechanism of action revealed that tubulysin, the cytotoxic payload of the ADC, induced cleavage of GSDME and elicited pyroptotic cell death in GSDME-expressing cells. Using GSDME KO, we showed that GSDME expression is critical for the effectiveness of the ADC as a monotherapy. Combining the ADC with Flt3L, a cytokine that expands dendritic cells in both lymphoid and non-lymphoid tissues, restored control of GSDME KO tumors.
conclusionsTogether, these results show for the first time that tubulysin and a tubulysin containing ADC can elicit pyroptosis, and that this fiery cell death is critical for antitumor immunity and therapeutic response.
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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.