<img height="1" width="1" src="https://www.facebook.com/tr?id=1582471781774081&amp;ev=PageView &amp;noscript=1">
  • Menu
  • crown-logo-symbol-1-400x551

Find it Quickly

Get Started

Select the option that best describes what you are looking for

  • Services
  • Models
  • Scientific Information

Search Here For Services

Click Here to Start Over

Search Here For Models

Click Here to Start Over

Search Here For Scientific Information

Click Here to Start Over

In Vitro

Boost oncology drug discovery with XenoBase®, featuring the largest cell line selection and exclusive 3D organoid models. Benefit from OrganoidXplore™ and OmniScreen™ for rapid, in-depth analysis.

Learn More

In Vivo

Enhance drug development with our validated in vivo models, in vitro/ex vivo assays, and in silico modeling. Tailored solutions to optimize your candidates.

Learn More

Tissue

Experience ISO-certified biobanking quality. Access top biospecimens from a global clinical network, annotated by experts for precise research.

Learn More

Biomarkers and Bioanalysis

Leverage our global labs and 150+ scientists for fast, tailored project execution. Benefit from our expertise, cutting-edge tech, and validated workflows for reliable data outcomes.

Learn More

Data Science and Bioinformatics

Harness your data and discover biomarkers with our top bioinformatics expertise. Maximize data value and gain critical insights to accelerate drug discovery and elevate projects.

Learn More

KRAS

Accelerate innovative cancer treatments with our advanced models and precise drug screening for KRAS mutations, efficiently turning insights into clinical breakthroughs.

Learn More

EGFR

Advance translational pharmacology with our diverse pre-clinical models, robust assays, and data science-driven biomarker analysis, multi-omics, and spatial biology.

Learn More

Drug Resistance

Our suite integrates preclinical solutions, bioanalytical read-outs, and multi-omics to uncover drug resistance markers and expedite discovery with our unique four-step strategy.

Learn More

Patient Tissue

Enhance treatments with our human tumor and mouse models, including xenografts and organoids, for accurate cancer biology representation.

Learn More

Bioinformatics

Apply the most appropriate in silico framework to your pharmacology data or historical datasets to elevate your study design and analysis, and to improve your chances of clinical success.

Learn More

Biomarker Analysis

Integrate advanced statistics into your drug development projects to gain significant biological insight into your therapeutic candidate, with our expert team of bioinformaticians.

Learn More

CRISPR/Cas9

Accelerate your discoveries with our reliable CRISPR solutions. Our global CRISPR licenses cover an integrated drug discovery platform for in vitro and in vivo efficacy studies.

Learn More

Genomics

Rely on our experienced genomics services to deliver high quality, interpretable results using highly sensitive PCR-based, real-time PCR, and NGS technologies and advanced data analytics.

Learn More

In Vitro High Content Imaging

Gain more insights into tumor growth and disease progression by leveraging our 2D and 3D fluorescence optical imaging.

Learn More

Mass Spectrometry-based Proteomics

Next-generation ion mobility mass spectrometry (MS)-based proteomics services available globally to help meet your study needs.

Learn More

Ex Vivo Patient Tissue

Gain better insight into the phenotypic response of your therapeutic candidate in organoids and ex vivo patient tissue.

Learn More

Spatial Multi-Omics Analysis

Certified CRO services with NanoString GeoMx Digital Spatial Profiling.

Learn More

Biomarker Discovery

De-risk your drug development with early identification of candidate biomarkers and utilize our biomarker discovery services to optimize clinical trial design.

Learn More

DMPK Services

Rapidly evaluate your molecule’s pharmaceutical and safety properties with our in vivo drug metabolism and pharmacokinetic (DMPK) services to select the most robust drug formulations.

Learn More

Efficacy Testing

Explore how the novel HuGEMM™ and HuCELL™ platforms can assess the efficacy of your molecule and accelerate your immuno-oncology drug discovery programs.

Learn More

Laboratory Services

Employ cutting-edge multi-omics methods to obtain accurate and comprehensive data for optimal data-based decisions.

Learn More

Pharmacology & Bioanalytical Services

Leverage our suite of structural biology services including, recombinant protein expression and protein crystallography, and target validation services including RNAi.

Learn More

Screens

Find the most appropriate screen to accelerate your drug development: discover in vivo screens with MuScreen™ and in vitro cell line screening with OmniScreen™.

Learn More

Toxicology

Carry out safety pharmacology studies as standalone assessments or embedded within our overall toxicological profiling to assess cardiovascular, metabolic and renal/urinary systems.

Learn More

Our Company

Global CRO in California, USA offering preclinical and translational oncology platforms with high-quality in vivo, in vitro, and ex vivo models.

Learn More

Our Purpose

Learn more about the impact we make through our scientific talent, high-quality standards, and innovation.

Learn More

Our Responsibility

We build a sustainable future by supporting employee growth, fostering leadership, and exceeding customer needs. Our values focus on innovation, social responsibility, and community well-being.

Learn More

Meet Our Leadership Team

We build a sustainable future by fostering leadership, employee growth, and exceeding customer needs with innovation and social responsibility.

Learn More

Scientific Advisory Board

Our Scientific Advisory Board of experts shapes our strategy and ensures top scientific standards in research and development.

Learn More

News & Events

Stay updated with Crown Bioscience's latest news, achievements, and announcements. Check our schedule for upcoming events and plan your visit.

Learn More

Career Opportunities

Join us for a fast-paced career addressing life science needs with innovative technologies. Thrive in a respectful, growth-focused environment.

Learn More

Scientific Publications

Access our latest scientific research and peer-reviewed articles. Discover cutting-edge findings and insights driving innovation and excellence in bioscience.

Learn More

Resources

Discover valuable insights and curated materials to support your R&D efforts. Explore the latest trends, innovations, and expertly curated content in bioscience.

Learn More

Blogs

Explore our blogs for the latest insights, research breakthroughs, and industry trends. Stay educated with expert perspectives and in-depth articles driving innovation in bioscience.

Learn More

  • Platforms
  • Target Solutions
  • Technologies
  • Service Types

Using Syngeneic Tumor Models for POC Studies

examples of proof of concept studies (poc studies) performed with syngeneic tumor models

examples of proof of concept studies (poc studies) performed with syngeneic tumor modelsSyngeneic tumor models are a predictive, high-throughput option for validating novel therapeutic approaches. Here’s how to use them for immuno-oncology agent proof of concept studies.

What Are Proof of Concept Studies?

Proof of concept (POC) studies aim to establish the feasibility of a novel therapeutic approach. These studies are generally conducted early on in clinical drug development, between Phase I and Phase IIa studies. POC studies are designed to test that a drug is active in a relevant system and shows evidence of efficacy in a clinically relevant endpoint.

Immunotherapy Proof of Concept Studies

Testing murine surrogate immuno-oncology agents requires a competent mouse immune system. This means that these POC studies can be carried out using syngeneic models or murine tumor cell lines within an immunocompetent host.

Why Use Syngeneic Models for POC Studies?

Syngeneic tumor models are a key platform in immuno-oncology drug development. We’ve previously discussed how to select the right syngeneic tumor model, design a meaningful study, and analyze the data generated.

The key applications of syngeneic models for immuno-oncology are Proof of Concept studies and target engagement studies to investigate mechanism of action (MOA) and pharmacodynamics (PD).

Using syngeneic models in POC studies provides a rapid, cost-effective approach to drug development with potential for high throughput. There is a wealth of knowledge and vast array of historical data available for comparison, which facilitates data interpretation. Furthermore, by harnessing the complexities of a competent immune system, any potential adverse effects involving, or amplified, by the immune system are detected early in your drug development process.

How to Use Syngeneic Models for Your POC Study

There are multiple ways syngeneic models can be used to support a POC study.

Syngeneic models are widely used to test a myriad of immunotherapy regimens. This includes:

  • Single agent immune checkpoint inhibitors (ICIs).
  • Combinations of multiple ICIs.
  • Combinations of ICI and immunogenic cell death inducers such as standard of care agents, radiation therapy, vaccines, and virotherapies.

Microbiome Research

The role of the microbiome in immunotherapy is another area of interest that can be explored using syngeneic models. Studies have shown that the intestinal microbiota may orchestrate immune responses. Therefore, by manipulating the microbiota, we may be able to modulate cancer immunotherapy. Syngeneic models allow easy collection of gut microbes at various points of your treatment regimen for further 16S rRNA sequencing.

Bioluminescent Imaging

Because syngeneic models are derived from immortalized cell lines, bioluminescent model variants can also be generated. This allows for real time evaluation of subcutaneous as well as orthotopic tumor progression and development of metastases by bioluminescent imaging.

Immunologic Memory

For therapeutic regimens that lead to complete tumor regression (e.g. non-palpable or detectable tumors), immunologic memory can be tested by re-challenging a cured animal. A corresponding age matched control animal is also implanted with cancer cells to compare tumor growth.

Testing Combination Regimes

Last, but not least, there are some extra things to consider when choosing a syngeneic model to test combination regimens. Looking at tumor growth inhibition (TGI) as an indicator of ICI sensitivity, and at baseline immunoprofiling, can help you choose the most appropriate models for your study. Partial responder or non-responder models are particularly useful when assessing combination strategy as the performance of the combination can be measured against single treatments.

Challenges in Using Syngeneic Models for POC studies

Understanding your model is the key to effective study design, and one thing to note about syngeneic models is the inherent variability in growth and response. The majority of models, such as B16-F10 and EMT-6, behave consistently with historic data. Some other syngeneics demonstrate higher variability, such as A20, MBT-2, and Pan02, and data obtained with these models need to be carefully analyzed and interpreted.

H22 Syngeneic Model Variability in Response

What makes things more complex is the intragroup variability – meaning some mice in a treatment group may respond while others may not. This is why it is important to look at individual mouse response using ‘spider plots’, shown here for the H22 model.

This variability is due to the complexity of the immune system and its interaction with the tumor in a living organism. Although mice used in syngeneic studies should all have the same genetic makeup, they each have their own unique immune signatures.

For example, mice that respond to treatment may have less myeloid derived suppressor cells (MDSCs) and upregulated levels of CD8+ effector T cells compared to non-responders. The observed intragroup variability can be exploited to look at PD markers, comparing responders and non-responders. This can provide you with an idea as to why the response may be different.

To compensate for this inherent variability, it’s important to structure a study so that you have sufficient ‘n’ per arm. This is because the statistical power increases with the number of mice. The other factor to consider is the estimated efficacy of the drug – the higher the efficacy, the less mice required to achieve statistical significance.

What Next? After Your POC Study

Overall, a thoughtfully designed POC study can set you on the path to clinical success.

Once you’ve confirmed the feasibility of your immunotherapeutic treatment regimen, the generated efficacy data can help guide the next phase of your study. A follow up study to interrogate the PD of your drug can reveal the MOA of your agent, and increase predictive power.

Additionally, you may want to select another model with specific characteristics, such as desirable growth curves and/or immune profile, to increase confidence with a reproducible response.


Related Posts