In Vivo Efficacy Evaluation

In vivo efficacy assessment is the most important indicator for evaluating drug therapeutic activity. Currently, the primary model for in vivo efficacy assessment of drugs, including cell therapy products, is the xenograft tumor model established on highly immunodeficient mice. Cyagen has developed a C-NKG mouse with independent intellectual property rights, which is ideal for establishing xenograft tumor models and human immune system reconstruction models, with T, B, and NK cells highly depleted. In addition, Cyagen has rich experience in constructing syngeneic mouse tumor models and has established a database of diverse tumor models. Therefore, Cyagen can provide customers with comprehensive and diverse in vivo efficacy assessment services.

Service Offerings

  • CDX tumor model based on immunodeficient mice such as C-NKG
  • Syngeneic tumor transplantation mouse model
  • Humanized mouse model of the immune system: PBMC and HSC humanization
  • mouse administration
  • In vivo efficacy monitoring
  • Biochemical testing of tissue samples

Cyagen’s In Vivo Evaluation Models

Model Types Model Names

Immunodeficient mouse models

 C-NKG mouse; NOD-Scid mouse; BALB/c nude mouse; SCID-Beige mouse

Humanized mouse models with reconstituted human immune system

 PBMC-humanized mouse; HSC-humanized mouse

Disease models

 Lung cancer model, Colorectal cancer model, Breast cancer model, Melanoma model, Liver cancer model, Gastric cancer model, Pancreatic cancer model, and more

CDX/PDX/homogeneous tumor mouse models

 Subcutaneous implantation model, Intraperitoneal implantation model, Tail vein injection model, Orthotopic implantation model

Why choose Cyagen?

Validated Models for Various Types of Tumors
  • Rich library of tumor cells and luciferase-labeled tumor cells
  • Comprehensive tumor modeling database covering solid tumors and hematological malignancies
  • Self-developed C-NKG mouse model with stable performance, high experimental repeatability, and reliable result data
  • High standard of animal experiment operation and breeding environment.
HIS Models
  • Different reconstruction methods using PBMC and HSC for high humanization
  • High survival rate and extended experimental duration for PBMC humanized mice
  • Good model homogeneity and more convincing data.
  • Different reconstruction methods using PBMC and HSC for high humanization

Case Study

  • Hematological Malignancy Models

Modeling of human acute lymphoblastic leukemia was performed on C-NKG mice and competitor mice by inoculating 200 μL of PBS (control group), 5×105 Luci-Nalm6 cells, and 1×106 Luci-Nalm6 cells. The figure on the right shows the in vivo imaging and average fluorescence intensity on the 21st day, demonstrating the successful modeling of human acute lymphoblastic leukemia. The growth rate of tumors in C-NKG mice was faster than in competitor mice.

 

Figure 1. In vivo imaging of small animals on the 21st day after tumor cell inoculation.

 

  • Solid Tumor CDX Model Construction

Cells were injected subcutaneously into C-NKG and NOD-Scid mice, and tumor volumes were measured at different time points. The cell injection dose was 5×106 per mouse, and data were presented as Mean ± SEM. The results showed that human liver cancer cells Huh7, human gastric cancer cells HGC-27, and human colorectal cancer cells SW620 were able to effectively establish tumor models in C-NKG mice.

 

Figure 2. Growth curve of Huh7 xenograft tumor after subcutaneous transplantation.

 

Figure 3. Growth curve of HGC-27 xenograft tumor after subcutaneous transplantation.

 

Figure 4. Growth curve of SW620 xenograft tumor after subcutaneous transplantation.

 

  • In Vivo Efficacy Evaluation Data of CD19 CAR-T Cells

Figure 5. Therapeutic effect of CD19 CAR-T cells on Nalm6 cell xenograft C-NKG mouse tumor model.

 

A. Experimental flow chart of CD19 CAR-T cell therapy on Nalm6 cell xenograft C-NKG mouse tumor model;

B. Results of PE live imaging monitoring of tumor growth, showing that CD19 CAR-T cells can inhibit tumor growth and prolong mouse survival;

C. Mouse survival curve;

D. Mouse weight growth curve.