With the continuous development of medicine, people's understanding of tumors is getting deeper and deeper, and the requirements for tumor models are getting higher and higher. The PDX (Patient-derived xenograft) model is increasingly favored by pharmaceutical companies and research institutes because of its close proximity to the patient's tumor genetic characteristics and heterogeneity (Fig 1). However, the PDX model is critical for immune-defective animals because it is subject to a heterologous graft immune response during construction.
Fig 1. PDX model maintains the heterogeneity and genetic characteristics of tumor tissues [1]
NOD-Scid mice as compared to nude,, B-NDG ® (NOD- Prkdc scid IL2rg tm1 / Bcgen) severe immunodeficient mouse model is a better choice PDX construct (Fig 2). B-NDG mice lack T, B, and NK cells, and have almost no rejection of human cells and tissues, which is more conducive to the growth of tumor tissues.
Fig 2. Advantages of B-NDG mice
Based on B-NDG mice, Baixuetu has successfully constructed more than 100 PDX models, including 3 cases of hematoma PDX model and 11 cases of breast cancer PDX model (Fig. 3).
Fig 3. PDX model that has been successfully built
Exon sequencing of the PDX model showed that the TTN, KMT2D and other gene mutation frequencies were higher in the solid tumor PDX model (Fig 4).
Fig 4. Solid tumor PDX exon mutant gene Top24
The PDX model of B-NDG mice is an ideal tool for detecting tumor efficacy after reconstruction of the human immune system. For different cancer types or different drug types, different models can be constructed for pharmacological efficacy testing.
Application example of constructing PDX model based on B-NDG mice
Three-negative breast cancer PDX model drug efficacy experiment
Triple-negative breast cancer (ER-/PR-/HER2-) accounts for 15%-20% of the total diagnosed breast cancer, because it has high tumor heterogeneity, high recurrence rate, early metastasis and poor prognosis. "The most difficult to treat breast cancer." At present, major pharmaceutical companies and research institutes are stepping up research and development on anti-three-negative breast cancer drugs. Bio-Syrah plans to construct a unique PDX model of triple-negative breast cancer for these diseases, and to carry out chemical drug efficacy test after immuno-reconstruction ( Fig 5) provides a strong model support for the study of drug development and treatment strategies.
Fig 5. Experiment on the efficacy of Sanyin Breast Cancer
The results showed that Drug X significantly inhibited tumor growth in the PDX model of triple-negative breast cancer compared with the control group.
Pharmacodynamic test of antibody-conjugated drug in gastric cancer PDX model
An antibody-drug conjugate (ADC) is an antibody drug that attaches a biologically active small molecule drug to a monoclonal antibody via a chemical bond. With brentuximabvedotin (SGN-35, trade name Adcetris) and Ado-trastuzumabemtansine (T-DM1, trade name Kadcyla) applied to cancer treatment, ADC drugs have once again become star drugs. The PX model of gastric cancer was constructed using B-NDG mice and the drug efficacy of ADC was tested after immunological reconstruction (Fig 6).
Fig 6. Efficacy experiment of gastric cancer antibody-conjugated drug
The results showed that compared with the PBS control group, the two ADC drugs tested and the positive control group inhibited the tumor growth in the PDX model mice to some extent. The PDX model based on B-NDG mice was used to study the antitumor efficacy of ADC. The ideal tool.
PDX due to its good heterogeneity and genetic characteristics will be the hot trend of future oncology development and preclinical efficacy trials of oncology drugs. Based on the PDX tumor model of B-NDG mice, Biotech is dedicated to the development of oncology in the fields of scientific research and medicine. For more information, please visit the official website of Biotech and we will be happy to help you.
references
[1] Sulaiman A, Wang L. Bridging the divide: preclinical research discrepancies between triple-negative breast cancer cell lines and patient tumors [J]. Oncotarget, 2017, 8(68): 113269.
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