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Updated: Jan 19, 2026
Method for Novel Anti-Cancer Drug Development using Tumor Explants of Surgical Specimens
Published on: July 29, 2011
Development of an Adrenocortical Cancer Humanized Mouse Model to Characterize Anti-PD1 Effects on Tumor
Julie Lang1, Anna Capasso2, Kimberly R Jordan1
1Department of Immunology & Microbiology, University of Colorado School of Medicine at Colorado Anschutz Medical Campus, Aurora, Colorado 80045.
Context:
Although the development of immune checkpoint inhibitors has transformed treatment strategies of several human malignancies, research models to study immunotherapy in adrenocortical carcinoma (ACC) are lacking.
Objective:
To explore the effect of anti-PD1 immunotherapy on the alteration of the immune milieu in ACC in a newly generated preclinical model and correlate with the response of the matched patient.
Design, Setting, And Intervention:
To characterize the CU-ACC2-M2B patient-derived xenograft in a humanized mouse model, evaluate the effect of a PD-1 inhibitor therapy, and compare it with the CU-ACC2 patient with metastatic disease.
Results:
Characterization of the CU-ACC2-humanized cord blood-BALB/c-Rag2nullIl2rγnullSirpaNOD model confirmed ACC origin and match with the original human tumor. Treatment of the mice with pembrolizumab demonstrated significant tumor growth inhibition (60%) compared with controls, which correlated with increased tumor infiltrating lymphocyte activity, with an increase of human CD8+ T cells (P < 0.05), HLA-DR+ T cells (P < 0.05) as well as Granzyme B+ CD8+ T cells (<0.001). In parallel, treatment of the CU-ACC2 patient, who had progressive disease, demonstrated a partial response with 79% to 100% reduction in the size of target lesions, and no new sites of metastasis. Pretreatment analysis of the patient's metastatic liver lesion demonstrated abundant intratumoral CD8+ T cells by immunohistochemistry.
Conclusions:
Our study reports the first humanized ACC patient-derived xenograft mouse model, which may be useful to define mechanisms and biomarkers of response and resistance to immune-based therapies, to ultimately provide more personalized care for patients with ACC.
Insights
Researchers developed a novel humanized mouse model for adrenocortical carcinoma (ACC) to study immunotherapy. This model showed that anti-PD1 therapy effectively inhibited tumor growth and enhanced anti-tumor immune responses in ACC.
Area of Science:
- Oncology
- Immunotherapy
- Preclinical Models
Background:
- Immune checkpoint inhibitors have revolutionized cancer treatment but lack research models for adrenocortical carcinoma (ACC).
- Effective immunotherapy strategies for ACC require robust preclinical models to study treatment responses and mechanisms.
Purpose of the Study:
- To establish and characterize a humanized patient-derived xenograft (PDX) mouse model for ACC.
- To evaluate the efficacy of anti-PD1 immunotherapy in this novel ACC model.
- To correlate preclinical findings with patient responses to immunotherapy.
Main Methods:
- Generation of a humanized mouse model using CU-ACC2 patient-derived xenograft cells.
- Treatment of mice with a PD-1 inhibitor (pembrolizumab).
- Assessment of tumor growth, immune cell infiltration (CD8+ T cells, HLA-DR+ T cells, Granzyme B+ CD8+ T cells), and comparison with patient data.
Main Results:
- The humanized model accurately reflected the ACC tumor.
- Pembrolizumab treatment significantly inhibited tumor growth (60%) in mice.
- Therapy increased tumor-infiltrating lymphocytes, including CD8+ T cells and Granzyme B+ CD8+ T cells.
- The treated patient achieved a partial response with significant tumor shrinkage.
Conclusions:
- The study presents the first humanized ACC PDX mouse model for immunotherapy research.
- This model can help elucidate mechanisms of response and resistance to immune-based therapies in ACC.
- The findings support the potential of immunotherapy for personalized ACC treatment.
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