Abstract 1269: Development of humanized PDX mouse model for high grade serous ovarian cancer
Notice bibliographique
Résumé
Abstract Introduction: High-grade serous ovarian cancer (HGSOC) is one the most lethal gynecological cancer, accounting for 70% deaths and with a 5-year survival rate below 50%. Traditionally, HGSOC are considered 'immune-cold' tumors, characterized by low immune infiltration and poor response rates to single agent immune checkpoint blockers (ICB). To improve the therapeutic potential of immunotherapies in HGSOC, combination treatments are being applied such as the Phase 2 MEDIOLA trial, which aims to identify mechanisms of response and resistance. A major challenge in this field remains the lack of suitable preclinical models for ICB-based treatments. Although patient-derived tumor xenografts (PDX) are valuable for developing new therapies, they are limited by the absence of an immunocompetent host. Here we present humanized mouse models incorporating human immune cells. Methods: Female NRG-W41-3GS mice (ENW) aged 7-8 weeks were used to generate the humanized PDX model. HGSOC tumors originally sourced from human patients and maintained in our laboratory’s previous PDX models using NRG mice, were injected subcutaneously into ENW mice. After 3 weeks, 5x104 human hematopoietic CD34+ cells collected from umbilical cord blood of healthy donors were intravenously injected via the tail vein. To monitor human cell engraftment, bone marrow (BM) aspiration was performed at week 6 post-CD34+ cell injection, and peripheral blood (PB) samples were collected from saphenous vein starting from week 7 until the experimental endpoint. BM and PB samples were analyzed by flow cytometry using antibodies against human CD45 and mouse CD45 to determine humanization level. Tumors were harvested at the endpoint, embedded in paraffin, and remaining tumor tissues were cryopreserved for future. To confirm human immune cell infiltration into the tumors, fresh frozen paraffin embedded tumor sections were immunohistochemically stained with rabbit anti-human CD45 antibodies. Results: We successfully generated sixteen huENW PDX mice. Robust engraftment of human CD34+ cells was confirmed in each mouse, with human CD45+ cells ranging from 35% to 90% (mean ± SD: 76.2 ± 18.5%) in BM samples and from 7% to 35% in PB samples. The huENW PDX model have revealed strong evidence of human immune infiltration with CD45+ cells on immunohistochemistry of the PDX tumors and spleen. Conclusion: Humanized mouse models offer a valuable resource for advancing HGSOC research. Our humanized PDX HGSOC mouse model demonstrated significant engraftment of human immune infiltration into HGSOC tumors. Future works will focus on characterizing tumor cell heterogeneity, analyzing spatial gene expression patterns and human immune cells distribution using Xenium in situ coupled with scRNA seq. We believe our model has the potential to enhance our understanding of HGSOC clonal diversity, microenvironment interactions, and contributing to the development of new therapies. Citation Format: Tsz Yin (Jacky) Lam, Farhia Kabeer, Shary Chen, Makoto Kishida, Yuchen Ding, Lorena Zoltan, Yvette Drew, David Huntsman. Development of humanized PDX mouse model for high grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1269.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».