huPBMC-MHC KO Mice

Alfa Cytology's huPBMC-MHC KO mice represent a significant advancement in humanized model technology, specifically engineered to address the challenge of graft-versus-host disease (GvHD). By utilizing major histocompatibility complex (MHC) knockout (KO) human PBMCs for engraftment, this model effectively delays the onset of GvHD, thereby extending the critical experimental window for in vivo efficacy studies. It is an ideal platform for researchers requiring longer-term observation, combination therapy evaluation, and exploratory studies that exceed the timeframe of conventional huPBMC models.

Introduction to huPBMC-MHC KO Mice

The huPBMC-MHC KO model is established by engrafting immunodeficient NCG or NSG mice with healthy donor-derived PBMCs in which major histocompatibility complex (MHC) molecules have been knocked out. This strategic modification significantly reduces the recognition of host mouse tissues by human T cells, the primary drivers of GvHD. While retaining the rapid setup and robust human immune cell reconstitution of the standard huPBMC model, the huPBMC-MHC KO variant provides a substantially extended treatment window. This allows for more complex study designs, including long-term dosing regimens, detailed pharmacodynamic assessments, and the evaluation of delayed immune responses.

Advantages of huPBMC-MHC KO Mice

Applications of huPBMC-MHC KO Mice

Case Study

Case 1: Superior Safety and Viability of the Second-Generation huPBMC-MHC KO Model

Overview

Directly compare in vivo tolerability, survival, and study window between a second-generation huPBMC–MHC-KO model and a traditional PBMC humanized model under a fixed therapeutic dosing regimen.

Study Information

• Humanized Model: Second-generation huPBMC-MHC KO mice.
• Control Model: Traditional humanized mouse model.
• Treatment: Administration of a therapeutic agent over a continuous two-week period.

Results

• Traditional PBMC model: Rapid peripheral human leukocyte reconstitution (hCD45⁺%) precedes dosing; following dosing, animals show progressive body-weight loss (percent change approaching substantial decline) and a marked drop in survival within the study window.
• Second-generation huPBMC–MHC-KO model: hCD45⁺% rises later; dosing was initiated ~7 days later to align with engraftment kinetics. After dosing, animals exhibit modest fluctuations in body weight and survival is maintained across the observation period.
• Study-window implication: Compared with the traditional PBMC model, the huPBMC–MHC-KO platform demonstrates better tolerability and preserved survival, enabling a more controllable and extended in-vivo study window under the tested regimen.

Fig.1 Tolerability and survival comparison between traditional PBMC humanized and second-generation huPBMC–MHC-KO models.

The huPBMC-MHC KO model is the definitive solution for preclinical studies that demand a longer and more stable experimental window. Alfa Cytology's Hu-Immune™ platform combines this advanced model with end-to-end services to empower your long-term immunotherapy research. Contact our scientific team now for customized solutions.

For research use only.