Suitable for Tumor Vaccines, Cell Therapy, and ADCC Research
The huHSC-NKG-ProF mice are an enhanced version of the huHSC-NKG series. The "Pro" indicates the upgraded series, while "F" stands for Full immune system reconstitution.This model is capable of generating a wide range of human immune cells, including lymphoid lineage cells (T cells, B cells, NK cells) and myeloid lineage cells (dendritic cells, monocytes, macrophages, granulocytes). Given their comprehensive immune cell reconstitution, these mice are also known as fully immune system humanized mice. They are ideal for immunology research, antibody-dependent cell-mediated cytotoxicity (ADCC) studies, and the development of tumor vaccines, cell therapies, and antibody-based drugs.
Construction Process
Research Applications
Autoimmune Diseases: This model is useful for evaluating the mechanisms and treatments of autoimmune diseases.
Drug Metabolism and Toxicity: This model is suitable for assessing the pharmacokinetics and toxicology of candidate compounds in vivo.
Validation Data
1)Sample type: Peripheral Blood
1. Humanized Level Post Human HSC Transplantation in NKG Mice:
Human umbilical cord blood-derived HSCs are transplanted into NKG mice for immune system reconstitution. The ratio of human CD45+ leukocyte to total CD45+ leukocyte can reach 40-60%.
2. Proportions of T Cells and B Cells Post Human HSC Transplantation in NKG Mice:
The T cell to human leukocyte ratio exceeds 30%, while the B cell to human leukocyte ratio ranges is from 10 to 20%.
3. Proportions of NK cells Post Human HSC Transplantation in NKG:
The NK cell to human leukocyte ratio range is from 20 to 40%, while the monocyte to human leukocyte ratio range in peripheral blood is from 1 to 3%. A higher ratio of the monocyte is observed in the splenocytes (see splenocyte data section).
4. Body Weight and Survival Rate Post Human HSC Transplantation in NKG:
2) Sample type: Splenocytes(14 weeks post human HSC transplantation)
1. Subsets of Humanized Immune Cells in the Splenocytes:
At 14 weeks post-transplantation of human umbilical cord blood-derived HSCs into NKG mice, splenocytes were harvested to analyze subsets of humanized immune cells. The ratio of human CD45+ leukocyte to total CD45+ leukocyte reached 50%. Among the human leukocytes, the proportion of T cells reached 40-50%, B cells reached 20% (higher than those in peripheral blood), NK cells reached 20%, and total human myeloid cells reached 20-25% (higher than those in peripheral blood).
2. Subsets of Human Myeloid Cells
In this mouse model, multiple human myeloid subtypes can be developed, including granulocytes, various types of monocytes (classical, intermediate, and nonclassical), and macrophages. In the absence of tumor implantation, M1 macrophages are predominant. However, following tumor implantation and with tumor progression, there may be a shift towards M2 macrophage polarization. Classical dendritic cells (cDCs) constitute 7% of the total myeloid cells, providing a foundation for antigen processing and presentation.
Pharmacodynamic Case Study
1. Case study: mRNA Tumor Vaccine for the Treatment of Melanoma
Following three administrations of the tumor vaccine, the inhibition rate of melanoma A375 tumors reached 38.75%. Antigen-specific T cell assays revealed a significant elevation in the proportions of Tetramer and IFN-γ in the vaccine-treated group. This indicates the presence of functional human T cells and dendritic cells in huHSC-NKG-ProF mice. Consequently, this mouse model can serve as an effective tool for preclinical efficacy studies of tumor vaccines.
2. Case study: Rituximab Treatment for Burkitt's Lymphoma
Following four doses of Rituximab, the tumor inhibition rate reached 77%, showcasing significant therapeutic efficacy. This finding suggests the presence of functional human NK cells in huHSC-NKG-ProF mice.
3. Case study: Autoimmune Disease - IBD Model
In this experiment, C57BL/6 and huHSC-NKG-ProF mice were fed with 3% DSS. After 7 days, both huHSC-NKG-Pr oF and C57BL/6 mice exhibited similar colitis phenotypes, including ulcers, mucosal damage, tissue edema, and and disruption of glandular structure. This finding indicates that huHSC-NKG-ProF mice can be used to construct a humanized colitis model. Further validation data is currently being collected.