ArticleJournal for immunotherapy of cancer2019
A novel anti-HER2 anthracycline-based antibody-drug conjugate induces adaptive anti-tumor immunity and potentiates PD-1 blockade in breast cancer.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 118 citations in OpenAlex.
- A phase II trial of nivolumab for patients with platinum-refractory recurrent or metastatic salivary gland cancer.Japanese journal of clinical oncology · 2026Trial
- First-line sacituzumab tirumotecan with tagitanlimab in advanced non-small-cell lung cancer: a phase 2 trial.Nature medicine · 2025Trial
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- Exploring the immunological effects of antibody-drug conjugates.Nature reviews. Clinical oncology · 2026Review
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- Sacituzumab Tirumotecan Across Gynecologic Malignancies: One Target, Multiple Diseases.Current oncology reports · 2026Review
- Spatiotemporally programmed nanomedicine engineering to resolve conflicting immunosignals in triple-negative breast cancer.Signal transduction and targeted therapy · 2026Article
- Immunogenic Cell Death: Unlocking New Frontiers in Cancer Immunotherapy.Cancer innovation · 2026Review
- SOT102, a novel CLDN18.2-targeting antibody-drug conjugate, exhibits strong therapeutic potential in solid tumors.BMC cancer · 2026Article
- Development of a STEAP1-Targeted Prostate Cancer Specific Antibody Drug Conjugate Platform with Immunostimulatory Properties.Research square · 2026Article
- Tumor cell death by ferroptosis contributes to an immunosuppressive tumor microenvironment in syngeneic murine models of cancer.Cancer & metabolism · 2026Article
- Consequences of the perivascular niche remodeling for tumoricidal T-cell trafficking into metastasis of ovarian cancer.ImmunoHorizons · 2026Article
- Antibody-Antibiotic Conjugates: Mechanisms, Clinical Progress, and Next-Generation Strategies Against Multidrug-Resistant Bacterial Infections.MicrobiologyOpen · 2026Review
- Comparative In Vitro Evaluation of Anti-HIV Immunotoxin, Antibody-Drug Conjugate, and Radioimmunoconjugate Targeted by the Same Antibody.Antibodies (Basel, Switzerland) · 2026Article
- Tumor cell death by ferroptosis contributes to an immunosuppressive tumor microenvironment in syngeneic murine models of cancer.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms of resistance to antibody-drug conjugates in cancer: molecular barriers and pharmacological solutions.Cancer chemotherapy and pharmacology · 2025Review
- Development of antibody drug conjugates targeting epithelial membrane protein 2-highly expressed lung cancer.Cell death & disease · 2025Article
- Overcoming immunotherapy resistance in bladder cancer with a novel antibody-drug conjugate RC48.Journal for immunotherapy of cancer · 2025Article
- Promising therapeutic efficacy and safety of a novel integrin α6-targeting peptide-drug conjugate in lung adenocarcinoma.Molecular cancer · 2025Article
- p95HER2, a truncated form of the HER2 oncoprotein, drives an immunosuppressive program in HER2Nature cancer · 2025Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increasing evidence suggests that antibody-drug conjugates (ADCs) can enhance anti-tumor immunity and improve clinical outcome. Here, we elucidate the therapeutic efficacy and immune-mediated mechanisms of a novel HER2-targeting ADC bearing a potent anthracycline derivate as payload (T-PNU) in a human HER2-expressing syngeneic breast cancer model resistant to trastuzumab and ado-trastuzumab emtansine. Mechanistically, the anthracycline component of the novel ADC induced immunogenic cell death leading to exposure and secretion of danger-associated molecular signals. RNA sequencing derived immunogenomic signatures and TCRβ clonotype analysis of tumor-infiltrating lymphocytes revealed a prominent role of the adaptive immune system in the regulation of T-PNU mediated anti-cancer activity. Depletion of CD8 T cells severely reduced T-PNU efficacy, thus confirming the role of cytotoxic T cells as drivers of the T-PNU mediated anti-tumor immune response. Furthermore, T-PNU therapy promoted immunological memory formation in tumor-bearing animals protecting those from tumor rechallenge. Finally, the combination of T-PNU and checkpoint inhibition, such as α-PD1, significantly enhanced tumor eradication following the treatment. In summary, a novel PNU-armed, HER2-targeting ADC elicited long-lasting immune protection in a murine orthotopic breast cancer model resistant to other HER2-directed therapies. Our findings delineate the therapeutic potential of this novel ADC payload and support its clinical development for breast cancer patients and potentially other HER2 expressing malignancies.
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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.