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Table 2 Different types, construction methods, characteristics, and applications of humanized mice

From: Generation, evolution, interfering factors, applications, and challenges of patient-derived xenograft models in immunodeficient mice

Mouse strain

Types of methods

Specific operation process

Advantage

Shortcoming

Immunotherapeutic applications

NOD/SCID IL-2Rγ C (NSG)

BALB/C Rag2 IL-2R γ C (BRG)

Humanized-PBMCs/Humanized-PBLs

Intravenous injection of PBMCs (5–10 × 106)

1. Cost effective;

2. Simple establishment;

3. Suitable for T-cell-related immune research

1. B, NK, and other immune cells fail to proliferate in vivo;

2. GVHD development;

3. EBV-associated lymphoproliferative;

4. Xenograft rejection

1. Adoptive NK and T cell therapy;

2. Tumor microenvironment evaluation;

3. CAR-T and NK cell therapy;

4. Immune check point inhibitor investigation;

5. Tumor-Infiltrating Lymphocyte therapy;

6. Gene therapy;

7. Dendritic cell therapy;

8. Targeted therapy;

9. Evaluation of microbiota-associated cancer treatment

NOG, NSG, NOD/SCID, BRG

Humanized-HSCs

(CD34+)

Intravenous injection of 1 × 105 HSCs

1. More complete immune reconstitution;

2. GVHD rarely occurs

1. Lack of T cells;

2. Limited sample sources

NOG, NSG, NOD/SCID, BRG

Humanized-BLT

Intravenous injection of CD34+ HSC (0.5–1 × 106) from human bone marrow, implantation of human fetal liver and thymus in to mouse sub renal capsule

1. Human T cells are restricted to human HLA;

2. Higher immune reconstitution;

3. Long term existence of model

1. GVHD development;

2. Engraftments should be carried from the same donor;

3. Complex technique and ethical problems;

4. Limited sample sources

MI(S)TRG, NSG

Genetic engineering

Human immune genes are knocked into respective mouse loci

Approximating the levels in the human system

Complex technique and expensive

  1. PBMCs peripheral blood mononuclear cells, PBLs peripheral blood lymphocytes, HSCs hematopoietic stem cells, BLT bone marrow, liver thymus