Approximately 400,000 people are diagnosed with kidney cancer annually. Kidney tumors are classified into different subtypes based on the cell of origin. Over 85% of malignant renal cell tumors are RCC, with the other 15% being nephroblastic, mesenchymal and metanephric tumors. The relatively high prevalence of RCC underscores the importance of developing novel treatments against renal cancer. However, to ensure that you obtain reliable data during the preclinical phase of your drug’s development, it remains important that well-characterized mouse models with known growth kinetics and/or response to standard-of-care treatments are used.
Syngeneic mouse models are an advantageous model due to their relative price and simplicity of experimental set-up compared to other models such as patient-derived xenografts (PDX). With the development of checkpoint inhibitors and the introduction of immunotherapy into medical oncology and RCC treatment, syngeneic models arise as suitable preclinical models due to the presence of a fully competent (murine) immune system. The most common syngeneic mouse model in RCC research is the murine syngeneic renal adenocarcinoma (RENCA) model. At InnoSer, RENCA is available both as a subcutaneous (Figure 1) and orthotopic model (Figure 2).
FIGURE 1. The subcutaneous RENCA syngeneic mouse model represents a simple, reproducible, well-established mouse model of RCC. Data show tumor growth curve data of the subcutaneous RENCA syngeneic mouse model of cancer in response to treatment with Doxorubicin (mean ± SEM). This model is particularly useful for preliminary screening tests of multiple compounds, as this model does not allow for efficacy studies into tumor microenvironment, vasculature and/or metastases.
FIGURE 2. The orthotopic RENCA syngeneic mouse model represents a more advanced mouse model of RCC, highly relevant in the context of immunotherapies. Following initial cell culturing, murine RENCA cells at different cell densities (10 000, 50 000, and 100 000 cells) were orthotopically injected. (A) Kidney weight (corrected for body weight) in mice orthotopically injected with the RENCA cells. Animals were sacrificed at first signs of tumor metastases. (B) Kidney volume in mice orthotopically injected with the RENCA cells. Animals were sacrificed at first signs of tumor metastases. Representative ultrasound imaging of (C) healthy kidneys and (D) kidneys with mice injected with RENCA cells. Kidneys of mice injected with RENCA cells lead to an increase in total kidney volume and development of lesions which can be longitudinally and non-invasively imaged and quantified. The orthotopic model is relevant to assess the efficacy of novel anti-RCC compounds in a model with native microenvironment, vasculature, and metastases.
At InnoSer, we are experienced with validating our clients’ cell lines to help determine the optimal seeding cell densities to induce stable and progressive in vivo tumour growth, enabling you to investigate your compound’s efficacy. Likewise, InnoSer’s team can include various standard-of-care compounds to serve as suitable comparators in your studies.
Syngeneic mouse models are advantageous to study immunotherapies. At InnoSer your research can be complemented by immune cell profiling studies using histopathology, flow cytometry as well as in situ multiplex immunohistochemistry. For some examples of analysis of flow cytometry, visit this page or multiplex immunohistochemistry please visit this page.
Interested in running a syngeneic mouse model study in different cancer types? InnoSer’s immuno-oncology team offers validated gold-standard mouse models of breast cancer (4T1), pancreatic (Panc02), melanoma (B16F10), peritoneal carcinoma (CC-531 adenocarcinoma) as well as colorectal carcinoma (MC38), among others. Reach out to our team here.