Robust and Cost-Effective Pharmacological Immunosuppression Enables Establishment of Nigerian Patient-Derived Xenograft (PDX) Models of Triple-Negative Breast Cancer (TNBC) in Low-Resource Settings

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Abstract

Background Genetically immunodeficient mouse models such as NOD/SCID and nude strains are widely used in cancer research for establishing patient-derived xenografts (PDXs). However, these models are expensive, require specialized facilities, and do not adequately reflect human immune-tumour interactions. This study aimed to develop a cost-effective and immunologically relevant pharmacological immunosuppression protocol in immunocompetent mice for the engraftment of triple-negative breast cancer (TNBC) xenografts in low-resource settings. Methods Female albino mice were treated with either cyclosporin A (35 mg/kg) plus ketoconazole (10 mg/kg) daily for five days, or cyclophosphamide (100 mg/kg) on alternate days (Days 0, 2, and 4). Haematological parameters, body weight, spleen weight, and feeding behaviour were monitored to assess immunosuppression and toxicity. A combined staged protocol was subsequently developed: cyclosporin A + ketoconazole for 5 days followed by cyclophosphamide (200 mg/kg on Day 6 and 100 mg/kg on Day 8), with orthotopic TNBC tissue implantation on Day 9. Results Cyclosporin A + ketoconazole significantly reduced total white blood cell, and lymphocyte counts by 65% and 75%, respectively (P < 0.05 and P < 0.01). Cyclophosphamide alone induced a 50% lymphocyte reduction with minimal toxicity. The combined protocol enabled a 30% tumour take rate at first passage (P0) and 80% at second passage (P1). Recapitulates equal expression of Molecular analysis confirmed over 80% similarity between xenografts and the primary tumour. Conclusion This is the first article which demonstrates breast cancer patient derived xenograft in Nigeria and a pharmacologically induced immunosuppression regimen can support effective TNBC xenograft establishment in immunocompetent mice. The protocol is robust, cost-effective, and more accessible than genetically modified models, making it well-suited for use in resource-limited research settings.

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