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Updated: Mar 18, 2026

Assessment of Chimeric Antigen Receptor T Cell-Associated Toxicities Using an Acute Lymphoblastic Leukemia Patient-Derived Xenograft Mouse Model

Assessment of Chimeric Antigen Receptor T Cell-Associated Toxicities Using an Acute Lymphoblastic Leukemia Patient-Derived Xenograft Mouse Model

Published on: February 10, 2023

Modeling Human Leukemia Immunotherapy in Humanized Mice.

Jinxing Xia¹, Zheng Hu², Satoshi Yoshihara³

¹Columbia Center for Translational Immunology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA; Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

|July 11, 2016

Summary

This summary is machine-generated.

A novel humanized mouse model spontaneously develops B-cell acute lymphoblastic leukemia (B-ALL). This model shows lymphopenia enhances immunotherapy efficacy, suggesting a potential treatment for leukemia patients.

Keywords:

Humanized mice Leukemia Lymphopenia Mixed-lineage leukemia fusion gene Recipient leukocyte infusion

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Area of Science:

Immunology
Oncology
Hematology

Background:

Current human tumor xenograft models require immunocompromised hosts.
There is a need for more advanced in vivo models for human cancer research.

Purpose of the Study:

To develop a humanized mouse model that spontaneously develops B-cell acute lymphoblastic leukemia (B-ALL).
To evaluate the efficacy of recipient leukocyte infusion (RLI) immunotherapy in this new model.

Main Methods:

Transplantation of human fetal thymic tissue and hematopoietic stem cells transduced with MLL-AF9 into mice.
Induction of B-ALL and subsequent immunotherapy studies using recipient leukocyte infusion (RLI).

Main Results:

The developed humanized mouse model exhibited spontaneous B-ALL development and was transplantable to secondary recipients.
Lymphopenia was found to significantly enhance the antitumor efficacy of RLI immunotherapy.
RLI demonstrated GVHD-free immunotherapy with antitumor responses and rejection of donor chimerism.

Conclusions:

The leukemic humanized mouse model is a valuable tool for studying leukemia immunotherapy.
Recipient leukocyte infusion (RLI) shows promise as a safe immunotherapy for leukemia patients, particularly those with severe lymphopenia.