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Hu CD34 Hematopoietic Stem Cell Reconstitution Mouse Model


Why do we need humanized mice?


There is a major obstacle to the evaluation of new human immunotherapies due to a lack of experimental models with a fully functional human immune system. Therefore, the development of humanized experimental models is an unmet need in immunotherapy research. As part of PharmaLegacy’s commitment to furthering immuno-oncology research, we have developed a humanized mouse model which harness the human immune system against human tumors.

The humanized mouse model can be used to provide: 

• A microenvironment that mimics human immune cell responses 

• An interaction between immune systems and tumor cells or tissues of human origin 

• A cost-effective platform to evaluate the effectiveness of potential new drugs to modulate the immune system without putting patients at risk


The development of CD34+ humanized mouse model

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We reconstitute NOG/NPG immunocompromised mice with a human hematopoietic system via engraftment of human cord blood CD34+ cells. The level of humanization is determined by human CD45+ cell ratio, which ranges from 40% to 60% with the majority of T and B cells in the peripheral blood after 16 weeks engraftment. Any mouse with >15% hCD45+ cells is considered as a valid model according to varies dosing studies. The CD34+ humanized mice have the longest research span of over a year without graft-versus-host disease.

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Level of “humanization” (human CD45+ cells ratio) ranged between 40%-60%, with little variation between batches of hCD34+ HSC transplanted animals.

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Level of human T cells reconstitution in peripheral blood increased continuously post hCD34+ HSC transplantation.


Availability of human tumor cell lines

Tumor Type

Cell Lines Validated

Tumor Type

Cell Lines Under Validation

Melanoma

A375

SK-MEL-5

NSCLC

EBC-1

NCI-H226

Epidermoid Carcinoma

A431

Melanoma

SK-MEL-28

A2058

Lung Cancer Cell

NCI-H1975

HCC-827

A549

Glioma

U251MG

Breast Cancer

HCC1954

MDA-MB-231

JIMT-1


Colon Cancer

HT29

Gastric Cancer

MKN45

NCI-N87

Lymphoma

Raji

Myeloma

RPMI8226

Glioma

U87MG


Case Study: Immune Checkpoint Inhibitors-Evaluating mAb PD-1/PD-L1 in HCC-827 Model

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Case Study: Immune Checkpoint Inhibitors-Evaluating mAb PD-1 in U87MG Model

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Case Study: Combination Therapy-Evaluating mAbs PD-1 and EGFR in HCC-827 Model

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Case Study: Bi-Specific Ab


Evaluating Bi-Specific Ab in NC1-N87 Model


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Evaluating Bi-Specific Ab in HCC827 Model

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Case Study: Oncolytic Virus


Evaluating Oncolytic Virus in HCC827 Model

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