ArticleCancer immunology, immunotherapy : CII2014
The microtubule-depolymerizing agent ansamitocin P3 programs dendritic cells toward enhanced anti-tumor immunity.
Article in Cancer immunology, immunotherapy : CII, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 76 citations in OpenAlex.
- Mirvetuximab soravtansine plus pembrolizumab in recurrent folate receptor alpha-positive uterine serous carcinoma: a phase II trial.Nature communications · 2026Trial
- Tumor biomarkers and efficacy in patients treated with trastuzumab emtansine + pertuzumab versus standard of care in HER2-positive early breast cancer: an open-label, phase III study (KRISTINE).Breast cancer research : BCR · 2023Trial
- Exploring the immunological effects of antibody-drug conjugates.Nature reviews. Clinical oncology · 2026Review
- Unveiling the molecular and immunological drivers of antibody-drug conjugates in cancer treatment.Nature reviews. Cancer · 2025Review
- Microtubules regulate tissue-level navigation in skin-resident macrophages.Journal of cell science · 2025Article
- Immunotherapy resistance in non-small cell lung cancer: from mechanisms to therapeutic opportunities.Journal of experimental & clinical cancer research : CR · 2025Review
- Promising therapeutic efficacy and safety of a novel integrin α6-targeting peptide-drug conjugate in lung adenocarcinoma.Molecular cancer · 2025Article
- Mechanism of action and future perspectives of ADCs in combination with immune checkpoint inhibitors for solid tumors.Clinical and experimental medicine · 2025Review
- Diagnostic and therapeutic advances for HER2-expressing or amplified gynecologic cancers.Gynecologic oncology · 2025Review
- Targeted drug conjugates in cancer therapy: Challenges and opportunities.Pharmaceutical science advances · 2024Review
- Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice.Experimental hematology & oncology · 2024Review
- The promise and challenges of combination therapies with antibody-drug conjugates in solid tumors.Journal of hematology & oncology · 2024Review
- Brentuximab Vedotin-Driven Microtubule Disruption Results in Endoplasmic Reticulum Stress Leading to Immunogenic Cell Death and Antitumor Immunity.Molecular cancer therapeutics · 2024Article
- Antibody drug conjugates: hitting the mark in pancreatic cancer?Journal of experimental & clinical cancer research : CR · 2023Review
- Antibody-drug conjugates in breast cancer: overcoming resistance and boosting immune response.The Journal of clinical investigation · 2023Review
- Targeting CD47-SIRPa axis shows potent preclinical anti-tumor activity as monotherapy and synergizes with PARP inhibition.NPJ precision oncology · 2023Article
- An anti-mesothelin targeting antibody drug conjugate induces pyroptosis and ignites antitumor immunity in mouse models of cancer.Journal for immunotherapy of cancer · 2023Article
- Global Regulator AdpA_1075 Regulates Morphological Differentiation and Ansamitocin Production inBioengineering (Basel, Switzerland) · 2022Article
- GPNMB: a potent inducer of immunosuppression in cancer.Oncogene · 2022Review
- Two strategies to improve the supply of PKS extender units for ansamitocin P-3 biosynthesis by CRISPR-Cas9.Bioresources and bioprocessing · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In addition to direct tumor cell cytotoxicity, chemotherapy can mediate tumor reduction through immune modulation of the tumor microenvironment to promote anti-tumor immunity. Mature dendritic cells (DCs) play key roles in priming robust immune responses in tumor-bearing hosts. Here, we screened a panel of 21 anticancer agents with defined molecular targets for their ability to induce direct maturation of DCs. We identified ansamitocin P3, a microtubule-depolymerizing agent, as a potent inducer of phenotypic and functional maturation of DCs. Exposure of both murine spleen-derived and human monocyte-derived DCs to ansamitocin P3 triggered up-regulation of maturation markers and production of pro-inflammatory cytokines, resulting in an enhanced T cell stimulatory capacity. Local administration of ansamitocin P3 induced maturation of skin Langerhans cells in vivo and promoted antigen uptake and extensive homing of tumor-resident DCs to tumor-draining lymph nodes. When used as an adjuvant in a specific vaccination approach, ansamitocin P3 dramatically increased activation of antigen-specific T cells. Finally, we demonstrate that ansamitocin P3, due to its immunomodulatory properties, acts in synergy with antibody-mediated blockade of the T cell inhibitory receptors PD-1 and CTLA-4. The combination treatment was most effective and induced durable growth inhibition of established tumors. Mechanistically, we observed a reduced regulatory T cell frequency and improved T cell effector function at the tumor site. Taken together, our study unravels an immune-based anti-tumor mechanism exploited by microtubule-depolymerizing agents, including ansamitocin P3, and paves the way for future clinical trials combining this class of agents with immunotherapy.
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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.