<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

Target to Lead Selection for ADCs and Biologics

Journey through the drug discovery pipeline from target discovery to in vivo pharmacology. Take advantage of the Largest biobank of patient-derived models, Model development capabilities, Cell-based assays for Screening ADCs, and advanced downstream analysis.

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

Preclinical Consulting Services

Learn more about how our consulting services can help to support your journey to the clinic.

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

Beginners Guide to PBMC Humanized Tumor Models

infographic of tumor bearing, PBMC humanized mouse model development

infographic of tumor bearing, PBMC humanized mouse model developmentDiscover PBMC-humanized tumor models for short-term immunotherapy assessment studies.

The Need for Humanized Models

As immuno-oncology continues to dominate cancer research, there’s an ever-increasing need for new and improved models for preclinical testing. When assessing the efficacy of human-specific agents, preclinical models with a human immune system are needed.

One approach, especially useful for short-term experiments, is PBMC-humanized tumor models.

What are PBMC Humanized Tumor Models?

PBMC-humanized tumor models combine huPBMC systems with cell line-derived xenografts. The resulting model is a human tumor-bearing mouse with a partially reconstituted human immune system.

Models humanized with PBMC are an alternative to costlier, full hematopoietic stem cell (HSC) reconstituted models, which can also be engrafted with human tumors.

How are PBMC Humanized Models Developed?

The starting point is an immunocompromised mouse strain, such as NOG®, NOD/SCID, or NCG. These different mouse strains have various levels of receptivity to PBMC, and a good knowledge of this can help to guide mouse selection for PBMC humanized tumor model development.

PBMCs, or peripheral blood mononucleated cells, are defined as any blood cell with a round nucleus, and include lymphocytes, monocytes, and macrophages. Ideally, fresh PBMC sourced from hospitals are used for humanization for a more patient-relevant analysis. Due to the inherent variability between human donors, at least two different PBMC donors should be used per developing model/inoculation.

Alternatively, PBMCs can be bought commercially, reducing variability and allowing you to go back to the same PBMC source for repeat studies.

The establishment of PBMC humanized tumor models requires optimization. This finds the right balance between tumor cell and PBMC concentration to allow sufficient tumor growth before an immune system reaction kicks in.

Optimization also includes finding the best inoculation route for both PBMCs and the tumor, for each individual PBMC/tumor combination. The human PBMCs can either be admixed or sequentially added to the immunocompromised mouse with the xenograft tumor of choice. PBMC administration routes include i.v. or i.p., or s.c. when admixed with tumor cells.

All of this results in optimal tumor engraftment paired with optimal immune cell reconstitution on a model-by- model, and even study-by-study basis. The final model is fully optimized, providing a human tumor within an animal with partially reconstituted human immunity, ready to test human-specific immunotherapies in vivo.

Which Immune Cell Populations are Reconstituted?

As noted above, these models provide partial human immune system reconstitution, so what exactly does this look like?

T and NK cell populations are reconstituted, which can be found in blood and tumor samples by FACS analysis. B cells are also reconstituted but are not necessarily identifiable in peripheral blood. This is because they are cleared faster than the T and NK cells.

In certain circumstances, under sensitization and challenge, B cell antigen response and antibody production are seen.

Which Cancer Indications are Available?

The choice of xenograft tumor model is limited by the development of graft vs host disease (GvHD) in this model type (discussed in more detail below). This means you need to use a tumor model which takes and grows within the short model timeframes available. Traditional cell line derived xenografts are therefore generally used.

Given the wide availability of human tumor cell lines, PBMC-humanized tumor models have been established for many cancer types. This includes breast, colon, esophageal, liver, lung, ovarian, prostate, and tongue cancer, as well as leukemia, lymphoma, and melanoma.

The inoculation route is often subcutaneous, although some orthotopic models are available. If the xenograft model you need isn’t already developed, this can often be created bespoke to meet your study needs.

What are the Strengths and Uses of PBMC Humanized Tumor Models?

Even with their complexities, PBMC humanized models are still a faster and simpler approach to humanization than HSC humanized systems. This means huPBMC tumor models can provide more cost-effective studies.

They are valid models for short term studies, or studies needing a high throughput. PBMC humanized tumor models are also useful for initial agent selection, stratification, or proof of concept validation before moving onto a full humanized study.

Models are already available and optimized for a range of solid tumors and blood cancers, often benchmarked with common immuno-oncology agents like immune checkpoint inhibitors.

Which Agents Can I Assess with PBMC Humanized Models?

PBMC humanized tumor models are useful to assess agents targeting T and NK cell function. This includes immune checkpoint inhibitors and agonists, T cell modulators, and bispecific T cell engagers, as well as NK modulating agents and those inducing ADCC. Cancer vaccines targeting B cell function can also be assessed.

What are the Challenges of PBMC Humanized Models?

PBMC humanized tumor models do come with some challenges, although these can be worked around and overcome.

As discussed above, variability can be an inherent issue when using fresh PBMC, because each individual’s PBMC provides an individualized response or lack of response. This is overcome by using at least two PBMC donors per study, and with studies being repeated with different donor pairs.

If using PBMC from hospitals, there can be an issue with repeat supply – a donor may not be available for repeat or new studies. Using commercial supplies can be a workaround, allowing you to revisit the same donor. Commercial PBMC are often supplied frozen, but model validation has shown that frozen PBMC produce comparable immune cell reconstitution to fresh PBMC.

Another challenge with using these models is the occurrence of graft versus host disease (GvHD). This is caused by human donor-derived immune cells responding to mouse antigens and occurs around three weeks post-huPBMC inoculation. This leaves you with a short treatment window – often from ten days to three weeks to complete an efficacy study.

GvHD should be taken into account before you start a study with this model type, and plays a role in the types of study you can perform. It means PBMC humanized tumor models are ideal for a short proof of concept study, but you wouldn’t use them for longer studies, say to test memory response or with slow growing tumors.

Improved models are being assessed to overcome GvHD, for example major histocompatibility (MHC) class I- and class II-deficient mice have been reported to have delayed GvHD development. Using these mice as the basis of the models could therefore expand the therapeutic window.

Summary

Multiple models exist for testing human-specific agents, from fully humanized, specific target humanized, to partially reconstituted PBMC humanized models. If you’re looking for a model for quick proof of concept and initial testing studies, then PBMC humanized models may be the best route to take.


Related Posts