Establishment of a humanized patient-derived xenograft mouse model of high-grade serous ovarian cancer for preclinical evaluation of combination immunotherapy
The limited efficacy of immunotherapy in clinical trials in high-grade serous ovarian cancer (HGSOC) may improve by implementing experimental models that are more reflective of human biology into preclinical studies. To address this, we developed and validated a humanized patient-derived xenograft m...
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| Autori principali: | , , , , , , , , , , |
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| Natura: | Article (Journal) |
| Lingua: | inglese |
| Pubblicazione: |
14 March 2026
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| In: |
Molecular oncology
Year: 2026, Pages: 1-17 |
| ISSN: | 1878-0261 |
| DOI: | 10.1002/1878-0261.70231 |
| Accesso online: | Verlag, kostenfrei, Volltext: https://doi.org/10.1002/1878-0261.70231
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| Note sull'autore: | Luka Tandaric, Line Bjørge, Martine Rott Lode, Cecilie Fredvik Torkildsen, Pia Aehnlich, Rammah Elnour, Daniela Elena Costea, Lars Andreas Akslen, Liv Cecilie Vestrheim Thomsen, Emmet McCormack and Katrin Kleinmanns |
| Riassunto: | The limited efficacy of immunotherapy in clinical trials in high-grade serous ovarian cancer (HGSOC) may improve by implementing experimental models that are more reflective of human biology into preclinical studies. To address this, we developed and validated a humanized patient-derived xenograft mouse model of HGSOC. Human hematopoietic stem cells and patient-derived HGSOC cells were engrafted into immunodeficient mice. The mice were administered durvalumab (anti-PD-L1) and/or oleclumab (anti-CD73) immunotherapy intraperitoneally twice a week for 5 weeks. The treatment showed good tolerability with no observed side effects, though it failed to elicit a measurable antitumor response. Leukocytes in primary tumors were analyzed immunohistochemically, and circulating T cells were characterized using spectral flow cytometry. All tumors exhibited an immune-excluded immunophenotype. No significant inter-group differences in disease burden, intratumoral leukocyte density, or circulating T cells were observed. In the durvalumab-only group, tumor burden significantly positively correlated with intratumoral cytotoxic and regulatory T-cell densities. This model reflects the immunotherapy resistance of human disease in line with clinical findings, providing a robust platform for studying tumor-immune interactions and immunosuppressive mechanisms in HGSOC. Impact statement Our results address the critical need for representative preclinical models for testing combination immunotherapy in HGSOC by providing a robust preclinical platform that can enhance the reliability of preclinical data and contribute to the improvement of the design and outcomes of future clinical trials. |
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| Descrizione del documento: | Gesehen am 21.05.2026 |
| Descrizione fisica: | Online Resource |
| ISSN: | 1878-0261 |
| DOI: | 10.1002/1878-0261.70231 |