Humanized patient-derived xenograft mouse model bearing ovarian clear cell carcinoma.

Abstract

Objective: The study aimed to establish humanized patient-derived xenograft (PDX) mouse models of ovarian clear cell carcinoma (OCCC) and evaluate their therapeutic responses.

Methods: PDX models and their humanized counterparts (CD34+ humanized PDX models) derived from the same tumor source were developed, and the therapeutic responses were compared between the models.

Results: Treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor significantly reduced tumor size in traditional OCCC PDX models (p=0.021). Although differences in tumor growth between traditional PDX models and humanized PDX models were observed, they were not statistically significant (p=0.438). However, treatment effects of PI3K inhibitor differed significantly between conventional and humanized mice (p=0.006). In the Humanized PDX cohort, both programmed cell death protein-1 antibody monotherapy and PI3K inhibitor treatment slowed tumor growth relative to controls, with a synergistic effect noted during the latter part of the study, though these effects were not statistically significant.

Conclusion: This pioneering study successfully develop a humanized PDX model for OCCC, highlighting differential responses to treatments compared to conventional PDX models.