From Target to Therapeutics with Humanized Mouse Models
Ever wondered how cutting-edge medical research translates lab findings into real-world treatments? At the forefront of this transformation are humanized mice. These lab partners are engineered to carry human elements such as DNA, cells, and immune systems, among others. By incorporating human biological components, humanized mouse models provide a more accurate simulation of human physiological responses, bridging the gap between lab research and clinical trials. Their crucial role allows researchers to achieve more reliable results, and accelerate the development of life-changing therapies.
Why Humanized Mouse Models Matter
Nearly 90% of drugs that enter phase 1 trials ultimately fail to reach the market. This does not account for the unknown failure rate during the preclinical phase. The difficulty in moving from preclinical results to successful human trials is often referred to as the “valley of death”. Conventional mouse models used in preclinical research often fall short in replicating the complexity of the human body, exacerbating the discrepancies between preclinical and clinical results. There is a critical need for advanced models that can more accurately simulate human conditions before moving on to costly and time-consuming clinical trials. This is where humanized mice come into play. Capable of expressing human proteins, exhibiting human immune responses, and developing human-like disease symptoms, humanized mice provide a more accurate representation of disease progression and treatment effects for preclinical research.
Creating humanized mice involves advanced engineering techniques. Traditionally, these mice are used to reconstitute the human immune system by transplanting human immune cells into mice that lack an immune response. This setup allows researchers to explore how the human immune system fights infections, influences disease progression, and reacts to immunotherapy.
Biocytogen’s Humanized Mouse Models
At Biocytogen, we aim to bridge the gap between lab findings and clinical studies by offering state-of-art humanized mouse models that go beyond traditional methods. In addition to providing immunodeficient mice for grafting human tissues, we have also developed drug target humanized mouse models by incorporating and replacing mouse genes with human ones. These models allow drug candidates to bind with humanized targets, enabling critical in vivo evaluations of drug efficacy, toxicity, and accurate pharmacokinetics/pharmacodynamics (PK/PD). They also support large-scale breeding and minimize variation among individual mice and experimental batches, ensuring consistency and reliability in preclinical studies. Our innovative models are at the forefront of advancing research and accelerating the development of new treatments.
Humanized Mice for Oncology Research
Humanized mouse models play crucial roles in oncology. A significant area of application lies in the study of immune checkpoints, which are molecules within the immune system that can either enhance or inhibit immune signals. Tumors often manipulate these checkpoints to shield themselves from attacks by the immune system. Checkpoint therapies therefore have been designed to normalize immune function, either by blocking inhibitory checkpoints or by activating stimulatory ones. Biocytogen has created and validated a series of humanized immune-checkpoint mice, enabling comprehensive in vivo evaluations of immune-checkpoint drug candidates. Biocytogen also provides humanized mice that target additional components such as tumor microenvironment (TME) modulators and tumor-associated antigens (TAA). Expanding our portfolio, we have introduced a series of dual/multi-target humanized mice focusing on key molecules such as PD-1/PD-L1, CD3E, 4-1BB, CD16A, and NKP46. These advanced models offer effective strategies for evaluating potential therapies, including antibody-drug conjugates (ADCs) and bispecific antibody treatments, accelerating the development of innovative cancer therapies.
Some example models at Biocytogen include:
- B-h4-1BB mice
- B-hPD-1/hPD-L1/h4-1BB mice
- B-hTNFR2 mice
- B-hPD-1/hPD-L1/hTNFR2 mice
- B-hCD73 mice
- B-hCD39 mice
- B-hPD-1/hCD39 mice
- B-hCCR8 mice
- B-hCD3E mice
- B-hCD3EDG mice
- B-hCD16A mice
- B-hTROP2 MC38 plus mice
Humanized Mice for Autoimmune Diseases
Autoimmune and inflammatory diseases present significant challenges and opportunities in new drug development. These conditions, which affect 5–8% of the population, encompass a variety of disorders each with distinct pathological mechanisms. To address these, Biocytogen has developed humanized mouse models specifically for autoimmune diseases such as asthma, atopic dermatitis, psoriasis, intestinal inflammation, and rheumatoid arthritis. These models focus on targeting relevant biomarkers, facilitating the development and testing of new therapeutic strategies.
Examples of our models include:
Humanized Mice for Metabolic Disorders
Metabolic disorders significantly impact human health, leading to chronic conditions such as diabetes and obesity. Driven by complex metabolic mechanisms that are not fully understood, these diseases are a major focus of medical research. Recognizing the critical need for advanced treatments and interventions to effectively manage these pervasive health issues, Biocytogen offers humanized mouse models targeting sugar and lipid metabolism. These are applicable to diseases such as diabetes, obesity, fatty liver, fibrosis, and arteriosclerosis. These models help researchers understand the complex mechanisms underlying these conditions and develop new treatments.
Examples of our metabolic disorder models:
Humanized Mice for Neurological Disorders
Neurological disorders affect more than 3 billion people worldwide and include a diverse range of conditions that impact the brain, spinal cord, and peripheral nerves. Notable examples include Alzheimer’s disease, Parkinson’s disease, autism spectrum disorders, and amyotrophic lateral sclerosis, among others. These conditions significantly impair cognitive, emotional, and motor functions, underscoring the critical need for intensive research and innovative drug development. By targeting specific biological pathways involved in the pathology of these disorders, Biocytogen has developed state-of-the-art humanized mice specifically engineered to advance research into these neurological conditions.
Examples of our models:
- B-hTAU mice
- B-hAPOE4 mice
- B-hTREM2 mice
- B-hLRP5 mice
- B-hTFR1 mice
- B-hIGF1R mice
- B-hTTR*V30M mice
- B-hCD98HC mice
Example analysis of strain-specific IGF1R expression in homozygous B-hIGF1R mice. Brain was collected from wild-type mice (+/+) and homozygous B-hIGF1R mice, and analyzed by flow cytometry with anti-IGF1R antibody. IGF1R was detectable in wild-type mice and homozygous B-hIGF1R mice, as the antibody is crossly reactive with IGF1R in human and mice. Human IGF1R was exclusively detectable in homozygous B-hIGF1R but not in wild-type mice.
Embark on a Journey of Discovery with Biocytogen
Didn’t find what you’re looking for? Beyond the models already mentioned, Biocytogen offers a variety of other humanized mice, including customizable options that allow researchers to tailor the mouse genome to specific research needs. By more closely mimicking human physiological responses, our humanized mice play a crucial role in transitioning from theoretical research to practical, life-saving drug development.
Contact us today to discover how Biocytogen’s humanized mouse models can advance your research!
References
Mullard, Asher. “Parsing clinical success rates.” Nature Reviews Drug Discovery 15.7 (2016): 447-448.
Seyhan, Attila A. “Lost in translation: the valley of death across preclinical and clinical divide–identification of problems and overcoming obstacles.” Translational Medicine Communications 4.1 (2019): 1-19.
Cogels, Morgane M., et al. “Humanized mice as a valuable pre-clinical model for cancer immunotherapy research.” Frontiers in oncology 11 (2021): 784947.
Dash, Prasanta K., et al. “Humanized mice for infectious and neurodegenerative disorders.” Retrovirology 18.1 (2021): 13.
Karnik, Isha, et al. “Emerging preclinical applications of humanized mouse models in the discovery and validation of novel immunotherapeutics and their mechanisms of action for improved cancer treatment.” Pharmaceutics 15.6 (2023): 1600.
National Stem Cell Foundation. “Autoimmune Disease”.
Steinmetz, Jaimie D., et al. “Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021.” The Lancet Neurology 23.4 (2024): 344-381.