Abstract 6121: Using the chicken chorioallantoic membrane in vivo model to study metastatic kidney cancer: A novel drug screening approach with more sustainable patient-derived xenografts

Abstract

Abstract Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancers. Annually, 74,000 Americans are newly diagnosed with the disease, and more than 14,000 patients succumb to death, especially due to the advanced-stage ccRCC developing distant metastases. Unfortunately, there is currently no effective therapy for the deadly stage. Despite the recent progress in immunotherapy or anti-angiogenesis kinase inhibitors, the efficacy varies from one patient to another. Therefore, gaining further insight into the metastatic mechanism and establishing more effective and personalized treatments are of an urgent need to overcome the deadly outcome of metastatic ccRCC. Patient-derived xenografts (PDXs) have been a great resource to study clinical cases for oncologic pathways and therapeutics. However, the cost and time to establish PDXs in immunocompromised mice, such as SCID mice, have been significant burdens. Here, we propose an alternative PDX in the chicken chorioallantoic membrane (CAM) model. This model has a short incubation time, an inherently immunodeficient state, direct tumor visibility, and is both cost and labor efficient in comparison to the traditional mouse model. In the pursuit to streamline the in vivo cancer research and drug development, we explored the feasibility of the CAM PDXs of metastatic ccRCC. First, we sought to develop an optimized protocol for engrafting ccRCC from patients into the CAM model. Patient specimens were implanted either as primary tumor cells or small pieces of tumor chunks. The rate of successful PDXs engraftment was incredibly high, at 70% or above. Our preliminary data using the established cancer cell lines validated the CAM model's ability to recapitulate the tumor biology, including the growth and metastasis, of both mouse and human cell lines. By implanting cells stably transduced with Firefly luciferase, bioluminescence imaging can be used for sensitive detection of tumor growth on the membrane. FDG-PET can also be performed, showing promises of the model for further implementation of imaging and therapeutics. Taken together, the CAM model serves as a valuable platform of novel PDXs to accelerate the study of tumor biology and the development of individualized medicine. Many of the advantages of this model, however, could potentially also be limitations. For example, the short incubation time and immunodeficient state complicate the observation and interpretation of therapeutic effects. To overcome these limitations and make the model more clinically relevant, we are trying to propagate PDXs over multiple generations of CAM, as well as to incorporate autologous immune cells from patients. With these flexible modifications, the CAM PDXs could be even more promising to advance personalized medicine and improve the adverse prognosis of metastatic ccRCC. Citation Format: Moe Ishihara, Junhui Hu, Celine Cano-Ruiz, Anthony Wong, Lily Wu. Using the chicken chorioallantoic membrane in vivo model to study metastatic kidney cancer: A novel drug screening approach with more sustainable patient-derived xenografts [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6121.