Clinically Predictive HIS Models for Human-Relevant Immunotherapy Validation
You’ve seen the statistics. Promising oncology drugs, years in the making, that fail the leap from preclinical promise to clinical reality. For immunotherapies, this translational gap is a chasm. Your innovative CAR-T cell therapy, your groundbreaking bispecific antibody, or your novel checkpoint inhibitor works beautifully in a conventional mouse model. But will it work in a human? More importantly, will it be safe? The fear that it won’t—that unforeseen toxicities like Cytokine Release Syndrome (CRS) will derail your program—can stall momentum and consume resources, leaving critical questions unanswered.
But what if you could close that gap? Imagine starting your next efficacy study with a model that doesn’t just carry human cells, but harbors a stable, multi-lineage human immune system. A system robust enough to evaluate long-term tumor responses and memory T-cell function. Picture a reality where you could accurately predict the risk of CRS before a human ever feels its effects, where your preclinical data provides not just a hint, but a clear, confident forecast of clinical performance. This isn't a future vision; it's the new standard for translational immuno-oncology.
From Aspiration to Application: A Human-Relevant System for Human-Centered Questions
Achieving this level of clinical predictability requires a model built from the ground up to overcome the trade-offs of the past. It demands an advanced platform that provides the stable, long-term engraftment of an HSC model with the robust, functional T-cell activity needed to mirror human immune responses. The Cyagen hu-HSC-NKG ProF™ mouse model was designed to be this solution, providing researchers like you with a reliable and clinically relevant in vivo platform.
By leveraging the severely immunodeficient NKG mouse and a proprietary dual-engraftment protocol, this platform delivers what researchers have long sought: a stable, predictable human immune system (HIS) model ready for complex, long-term studies. This isn't just an incremental improvement; it's a new capability for your lab.
- High-Fidelity Human T-Cell Reconstitution: Move beyond models with weak or inconsistent T-cell function. Our optimized approach consistently achieves greater than 55% hCD3+ T-cell populations in peripheral blood, ensuring the primary drivers of anti-tumor immunity are present and functional.
- Stable, Long-Term Engraftment: Forget the 4-6 week limitations of PBMC models. The hu-HSC-NKG ProF™ provides a stable human immune system for over 24 weeks, enabling long-term efficacy studies, memory response evaluation, and chronic toxicity assessments that were previously impossible.
- Comprehensive Multi-Lineage Immunity: Your therapy won’t just interact with T-cells. Our models display robust reconstitution of human B-cells, monocytes/macrophages, and dendritic cells, creating a more complete immunological environment to study complex mechanisms of action and off-target effects.
- Clinically Relevant CRS Prediction: With a functional human immune system capable of producing human-specific cytokines, you can accurately model the mechanisms of CRS. Test the safety of your biologics and develop mitigation strategies with confidence, knowing the data reflects a human-like response profile.
- Ready When You Are: We’ve eliminated the bottleneck of model creation. Instead of waiting a year to build your own cohort, you can access off-the-shelf cohorts of fully reconstituted HIS mice, allowing your team to move directly from hypothesis to experimentation.
A Partnership Built on 19 Years of Model Innovation
For nearly two decades, we have partnered with labs at the forefront of biomedical research, navigating the complexities of in vivo model design. This journey has taught us that true progress comes from building tools that directly solve the core challenges holding researchers back. The development of our HIS model portfolio is a direct result of listening to the frustrations of immunologists and oncologists who needed a better way to bridge the preclinical-to-clinical divide.
The evidence of this partnership is in the data. Researchers using our hu-HSC-NKG ProF™ platform are not just observing engraftment; they are achieving results with direct clinical implications. In head-to-head studies, our models have demonstrated their predictive power in evaluating leading immunotherapies:
- mRNA Tumor Vaccine for Melanoma (A375): The huHSC-C-NKG-ProF™ mice showed a 38.75% tumor inhibition rate after mRNA tumor vaccine treatment for A375 melanoma. The vaccine treatment group also exhibited a significant increase in Tetramer and IFN-γ ratios in antigen-specific T-cell detection, indicating the presence of functional human T cells and dendritic cells in the huHSC-C-NKG-ProF™ mice. This model can serve as an effective tool for preclinical tumor vaccine efficacy studies.
- Rituximab Treatment for Burkitt's Lymphoma (Raji): Treatment with Rituximab in huHSC-C-NKG-ProF™ mice resulted in a 77% tumor inhibition rate after four doses, demonstrating significant therapeutic efficacy. This suggests that the huHSC-C-NKG-ProF™ mice possess functional human NK cells.
- Inflammatory Bowel Disease Model: When fed with 3% DSS, huHSC-C-NKG-ProF™ mice developed similar colitis phenotypes to C57BL/6 mice after 7 days, including ulcers, intestinal mucosal damage, tissue edema and congestion, and glandular structure destruction. This indicates that the huHSC-C-NKG-ProF™ model can be used to construct humanized colitis models.
These outcomes represent more than just successful experiments. They represent a reduction in risk, an acceleration of timelines, and a newfound confidence in translational data. By providing a model where human immunity can be studied with unprecedented stability and functional depth, we empower our partners to make better, more informed decisions on the path to the clinic.
Take the Next Step on Your Translational Journey
The path to clinical success is challenging, but you don't have to walk it with uncertain data. The right preclinical model transforms your research from a series of experiments into a clear, predictive narrative. It’s time to stop compromising with models that create more questions than answers and start working with a system designed for human-relevant results.
Let us help you design a study that delivers the clarity you need. Whether you are evaluating a novel CAR-T therapy, a multi-specific antibody, or an autoimmune modulator, the journey to confident clinical translation starts here.
Explore our validated, off-the-shelf HIS model cohorts ready for your next study.
Or, schedule a consultation with our scientific strategists to discuss a custom model design tailored to your unique research goals.
