PBMC-engrafted Humanized In Vivo Mouse Model

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

As immuno-oncology continues to dominate cancer research, there is 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. To date, humanized peripheral blood mononuclear cells (PBMCs) mice model has the fastest engraftment rate using adult PBMCs and enables short-term studies requiring a strong effector and memory T cell function. Creative Biolabs presents an innovative and cost-effective platform to offer PBMC-engrafted humanized in vivo mouse model for cytokine release syndrome (CRS), T cell immune modulation, infectious diseases and graft rejection research.

Introduction

Immunotherapy is a powerful treatment strategy being applied to different kind of diseases such as cancer, autoimmune diseases, allergies, and transplantation. Although these therapies have demonstrated significant clinical efficacy, there is also the potential for severe adverse events, including CRS. CRS is characterized by the rapid production of inflammatory cytokines following delivery of therapy. Unfortunately, the animal models and in vitro human PBMC assays presently in use can't reliably predict the CRS in patients.

Current platforms to screen biologic agents for induction of CRS include in vitro studies with human PBMC and in vivo animal models. However, there is still an urgent need for human-based in vivo CRS screening platforms that are accurate, translatable, can easily be scaled and will ideally enable the study of patient-specific responses. Humanized mouse models provide a potential translational bridge for the study and prediction of CRS in vivo.

Human PBMC mouse model.

Fig.1 Human PBMC mouse model. (De La Rochere, 2018)

PBMC Humanized Mice Accelerate Drug Discovery and Development

Humanized mice are developed by injecting PBMCs into immunodeficient mice, such as NSG, NOG and BRG mice. PBMC engraftment supports short-term studies, creating transient, partially-reconstituted human immunity. To address the gap between pre-clinical testing and clinical trials, PBMC-engrafted humanized in vivo mouse models have been used for quantitating CRS. Generally, PBMC-engrafted NSG, NSG-MHC-DKO, and NSG-SGM3 mice were used to study cytokine release in response to treatment with mAb immunotherapies. These humanized in vivo mouse models enabled the detection of cytokine release stimulated by several mAbs and are rapid, sensitive, and reproducible platforms to screen novel therapeutics for inflammatory events.

Services at Creative Biolabs

PBMC-engrafted Humanized In Vivo Mouse Model PBMCs humanized mouse models that most closely mimic the human immune system provide an in vivo platform for immuno-oncology and cell therapy. Prediction of therapeutic efficacy and success is more accurate when using such models and should be a cornerstone of your cell and gene therapy in vivo testing program. Creative Biolabs has partnered to provide you with the tools you need to efficiently incorporate humanization studies into your workflow.

Benefits of the PBMC Humanized Mouse Model in CRS Research

Convenient - Ready-to-use PBMCs are pre-injected and tested for effective engraftment in the mouse model.
Efficient - Pre-screened PBMCs save time, labor, and costs associated with donor qualification.
Quality - PBMC cell inventory has been screened for engraftment rate, body weight loss, and study term. Cell numbers have been optimized for use in the mouse model.

Features

Quality primary cells for engraftment
Optional mouse model
Strategic planning
Cytokine profiles analysis in the PBMC-engrafted mouse model
Evaluation of cytokine release
Comparison of cytokine release using the in the PBMC-engrafted in vivo mouse model and an in vitro PBMC assay

Please contact us for more information about our PBMC-engrafted humanized mouse model products or services.

Reference

De La Rochere, P.; et al. Humanized mice for the study of immuno-oncology. Trends in immunology. 2018, 39(9): 748-763.