“Gasping for breath, chest tightness and shortness of breath… ” This is the common problem faced by 358 million asthma patients worldwide. As a complex chronic airway inflammatory disease, the pathogenesis of asthma is still not fully understood, and drug development also faces numerous challenges. And animal models are precisely the key “key” to solving this problem.
Today, we will focus on introducing a “golden tool” specifically designed for asthma research – the OVA-induced B-hTSLP/hTSLPR plus asthma animal model.
1、First understand the two key points: OVA induction and humanization of TSLP/TSLPR
Ⅰ. OVA induction: The “classic gold standard” for asthma models
OVA, also known as ovomucoid protein, is a commonly used allergen in scientific research. Using it to establish an asthma model has become the “gold standard” recognized within the industry. The core principle is quite simple and involves two steps: “allergen exposure – trigger”.
• Allergic stage:Inject OVA + adjuvant into the abdominal cavity of mice to enable the immune system to “remember” this foreign substance, activate the Th2 type immune response, and produce specific IgE antibodies.
• Inspiration Stage:一After a certain period of time, the mice were exposed to OVA again through aerosol inhalation, triggering the immune system’s “counterattack”, thereby causing typical asthma symptoms such as airway inflammation and excessive mucus secretion.
The advantages of this method are quite remarkable: the OVA components are clear, the source is stable, the experiment is highly reproducible, and it can also be adjusted according to the needs to simulate different types of asthma inflammatory phenotypes.
Ⅱ. B-hTSLP/hTSLPR plus：A more human-like “humanized upgrade”
If OVA induction serves as the “basic framework”, then the humanization of TSLP/TSLPR is the “core upgrade point” of this model.
• TSLP (thymic stromal lymphopoietin) is a cytokine secreted by epithelial cells, and TSLPR is its receptor. Once the signaling pathway of this “pair” becomes disrupted, it can trigger various inflammatory diseases such as asthma and allergic dermatitis, and has become a popular target for asthma treatment in recent years.
• The B-hTSLP/hTSLPR model, in simple terms, involves replacing the mouse’s own TSLP and TSLPR genes with their human counterparts. As a result, the mice will express functional human TSLP and TSLPR proteins, which can perfectly simulate the relevant signaling pathways in humans, making drug evaluation more closely resemble clinical reality.
2、Three core advantages unlock new possibilities in asthma research
By combining the “classic gold standard” with the “humanized upgrade”, the advantages of this model are fully realized, and it has solved many problems of the traditional models:
Advantage 1: Dual humanization, leading to more accurate efficacy assessment
• Unlike single-target humanized models, this model achieves dual humanization of TSLP and TSLPR, perfectly replicating the human TSLP-TSLPR signaling axis. This means that antibody drugs targeting the human TSLP/TSLPR targets (such as the clinically used Tezepelumab) can be precisely validated for their efficacy in this model, providing more reliable data support for preclinical research.
Advantage 2: The disease phenotype is stable, and the simulation is more comprehensive.
• After verification, this model can consistently exhibit the core characteristics of asthma after OVA induction: airway hyperresponsiveness, eosinophil infiltration, elevated serum IgE levels, and excessive airway mucus secretion. Moreover, it can simulate Th2-type inflammatory responses, which are more in line with the pathological features of human allergic asthma, providing an ideal platform for mechanism research.
Advantage 3: Stable immune system, wide range of application scenarios
• The distribution of immune cells and cytokine profiles of the model are similar to those of wild-type mice, and the immune system is stable. Besides being used for the efficacy evaluation of asthma drugs, it can also be applied in various scenarios such as the study of the TSLP-TSLPR signaling pathway mechanism, the in vivo validation of antibody drugs, and the assessment of drug safety. It offers extremely high cost-effectiveness.
3、Summary of applicable scenarios
• Research on the pathological mechanism of allergic asthma, particularly the role of the TSLP-TSLPR signaling pathway;
• Preclinical efficacy assessment of antibody drugs and small molecule drugs targeting the human TSLP/TSLPR target.
• Verification of the mechanism of action of asthma treatment drugs (such as inhibiting the infiltration of inflammatory cells, reducing IgE levels, etc.);
• Screening and optimization of new asthma treatment plans.
The KCI•KMQ Respiratory System Disease Pharmacology and Efficacy Evaluation Platform has a comprehensive animal model system. The platform has accumulated rich project experience and can meet diverse research needs. Currently, the company has established extensive long-term cooperation with many well-known pharmaceutical enterprises and research institutions at home and abroad, providing a solid foundation for the development of innovative drugs.
Data presentation
• Changes in animal body weight, lung weight and lung index
The lung weight of the model control group animals was significantly higher than that of the normal control group animals. After treatment with Tezepelumab, the lung weight was significantly reduced.
• Airway hyperresponsiveness test（Penh）
Twenty-four hours after the last OVA stimulation, the airway responses of the animals exposed to different doses of acetylcholine (Methacholine, MCh) were measured using a non-invasive pulmonary function instrument.
• Flow cytometry for detecting inflammatory cells in BALF
At the end of the experiment, bronchoalveolar lavage fluid (BALF) was collected to detect inflammatory cells. The results showed that the CD45+ cells and eosinophils in the model group were significantly higher than those in the normal control group. After treatment with Tezepelumab, these cells were significantly reduced compared to the model control group.
• Serum total IgE and OVA-specific IgE detection
The total IgE and OVA-specific IgE levels in the serum were detected by ELISA. The results showed that compared with the normal control group, the total IgE and OVA-specific IgE levels in the serum of mice induced by OVA significantly increased. After treatment with Tezepelumab, the total IgE and OVA-specific IgE levels in the mice decreased significantly.
• Organ pathology HE test results
The OVA-induced B-hTSLP/hTSLPR plus asthma animal model mainly presents inflammation in the bronchi and pulmonary small arteries of the lungs. After treatment with Tezepelumab, the inflammation significantly improved.
• Organ pathology PAS test results
The OVA-induced B-hTSLP/hTSLPR plus asthma animal model showed that the goblet cells in the bronchial mucosa layer proliferated and mucus deposition occurred. The PAS staining results showed that the positive area per unit length was significantly increased in the model group, and it significantly decreased after treatment with Tezepelumab.
The value of animal models: A crucial bridge from mechanism analysis to clinical translation
The key challenge in asthma research lies in the complexity and variability of its pathological mechanisms. The asthma animal model induced by KCI•KMQ OVA and featuring B-hTSLP/hTSLPR is not only reliable like the traditional models but also upgraded with humanization to closely resemble clinical reality. It provides researchers with more precise and comprehensive research tools, injecting new impetus into asthma research.
Exploring diseases, empowering research. We are committed to using reliable models and data to facilitate the emergence of the next generation of therapies.
KCI Biotech and its wholly-owned subsidiary, KMQ Biotech and KAL Biotech are CROs specializing in providing preclinical pharmacodynamics and durability evaluation services for pharmaceutical research and development. The company owns AAALAC-accredited state-of-the-art laboratory animal facilities in Suzhou and Nantong,with a total area of more than 40,000m²,which can meet the needs of various types of preclinical research. The company has a full range of laboratory animal platforms including rats, mice, hamsters, guinea pigs, rabbits, cats, ferrets, dogs, pigs, sheeps and non-human primates. The in vivo pharmacolofical department supplies more than 400 animal disease models for human medicine development research. The BSL2/ABSL2 department supplies more than 100 pathogenic microorganisms, including bacteria, viruses, and fungi for human medicine development research, veterinary medicine and pet medicine. The company also supplies pathology, toxicology, pharmacokinetics, cellular and molecular biology, and medical imaging services. The company has already cooperated with more than 1,000 famous domestic and international pharmaceutical companies , and completed more than 2000 domestic and international projects .
With a professional R&D team, rich experience in in vivo pharmacology and pharmacodynamics evaluation, and a professional spirit of integrity and excellence, KCI/KMQ/KAL will provide a full range of preclinical drug discovery and development services for global pharmaceutical companies and research institutions, and establish a professional and efficient drug discovery and evaluation system.
