World Cancer Day: Features of Popular Tumor Models in Oncology Drug Development

According to data released by the International Agency for Research on Cancer (IARC) of the World Health Organization, China ranks first in the world in both cancer incidence and mortality.

At present, the etiology of malignancy is still not fully understood. The determinants include both exogenous factors (living habits, environmental pollution, occupation, natural and biological factors, chronic stimulation and trauma, and iatrogenic factors, etc.) and endogenous factors (genetic factors, immune factors, and endocrine factors, etc.). Therefore, the treatment methods are not only varied, they could be limited for some cancers.

February 4th is the 24th World Cancer Day. Medicilon has been part of the great human effort to combat cancer since its founding in 2004. In order to better understand tumorigenesis, to foster cancer prevention and to develop novel anti- cancer therapy, Medicilon has been providing IND enabling preclinicalservice for 19 years, and has established close to 300 tumor evaluation model for R&D.

For example, we have completed model establishment and efficacy evaluation for immuno- and genetherapies, such as CAR-T, TCR-T, CAR-NK, oncolytic virus, antibody (monoclonal antibody, bispecfic antibody, polyclonal antibody), siRNA, AAV.  Below are some examples representing such capability.

1、PDX Models

Patient-Derived Tumor Xenograft Model (PDX): This model is established by directly transplanting the patient's tumor tissue into immunodeficient mice. The characteristics of most primary tumors retain regarding histopathology, molecular biology and gene level, ensuring relatively reliable predictions of clinical efficacy. Therefore, the platform is widely used in the development of new drugs, especially in the selection of patients in clinical trials of target drugs and the study of predictive biomarkers.

Establishment of PDX model^[1]

Patient-Derived Tumor Xenograft (PDX) model retains the characteristics of patients’ tumor tissues and features more clinical relevance. Combined with humanized mice, such models (see below) can facilitate optimal evaluation of anti-tumors related to immuno-oncology.

2、Syngeneic Mouse Models

Syngeneic models are transplantation models obtained by injecting a recipient of a specific genetic background with cell lines previously established through isolation of tumor cells from a mouse of the same genetic background.

The syngeneic mouse model allows studying cancer under a complete immune system, which is essentially for immunotherpay evaluation.  We can provide various syngeneic models to test the effectiveness of drugs according to our clients' requirements. Typical syngeneic disease models include those for breast cancer, lung cancer, colon cancer, kidney cancer, diffuse large B-cell lymphoma (DLBCL), etc., in mice, rats and hamsters.

A list of examples of syngeneic models established in Medicilon.

3、Orthotopic Cancer Models

The orthotopic cancer models focus on the impact of the interaction between tumor cells and their surrounding interstitial organ microenvironment. Therefore, orthotopic tumor models are often compared with subcutaneous tumor models.

The only disadvantage is that the establishment of an orthotopic tumor model is more morecomplicated and requires fluorescent labeling imaging or bioluminescence in vivo imaging to detect tumor growth.

Medicilon Pharmacology & Pharmacodynamics Lab is equipped with advanced instruments such as IVIS® Spectrum In Vivo Imaging System and IVIS® Lumina III In Vivo Imaging System We overcome the technical barriers of experiments with experienced in vivo scientists, and have established many orthotopic transplantation models, including those for cancers originated in brain, liver, lung, tibial bone marrow cavity, and intravesical orthotopic transplantation.

Orthotopic brain tumor models

Ovary carcinoma models

Lung tumor models

Tibia marrow cavity tumor models 

With the rapid development of science and technology, the development of tumor models is also advancing with the times. In addition to these models described in this article, there are also tumor research models such as spontaneous models, induced models, and genetically modified models.

Medicilon continues to align our capability development and our mission with the cancer research field and actively participates in world-wide cancer conference. For example, our presence and participation in the annual meeting of the American Association for Cancer Research (AACR) have been for many years, aiming to promote the exchange and dialogue of new knowledge and new ideas among scientists in the field of cancer research, and to improve public awareness of cancer.

References：

[1] SNI:Neuro-Oncology 2015, Vol 6, Suppl I - A supplement to Surgical Neurology International

[2] Gould, S. E., Junttila, M. R., & de Sauvage, F. J. (2015). Translational value of mouse models in oncology drug development. Nature Medicine, 21(5), 431-439.