Mouse Models for Immunotherapy in Hepatocellular Carcinoma
<p>Murine models for immunotherapy studies of HCC. (<b>A</b>) Syngeneic mouse models: Mouse tumor cells are implanted in immune-competent mice. (<b>B</b>) Chemotoxic agent mouse models: Chemicals are administered to induce HCC growth. (<b>C</b>) Genetically engineered mouse models: Tumor suppressor gene deletion or oncogene activation is built into mice. (<b>D</b>) Human cell line and patient-derived xenograft in humanized mouse models: Human peripheral blood mononuclear cells (PBMC) or human CD34<sup>+</sup> cells are given to immunodeficient mice. (PDX, patient-derived xenografts; Hu-PBL, PBMC-humanized mouse model; HSC, hematopoietic stem cells).</p> "> Figure 2
<p>Equipment or methods used for in vivo tumor monitoring. Micro-PET, Micro-CT, MRI, ultrasound, and bioluminescence are the commonly used methods for monitoring tumors non-invasively. Besides the imaging of tumors and surrounding tissues that they can provide, based on their imaging mechanism, other parameters can be provided to determine the status of a tumor. For example, the blood flow and the hypoxic regions can be used to identify the degree of angiogenesis in a tumor. Biopsy (and liquid biopsy) are also methods used for monitoring tumors, with analysis of the cells (tumor or immune cells), proteins, DNA, or any detectable tumor-related marker being used to understand or predict the tumor condition.</p> ">
Abstract
:1. Introduction
2. Syngeneic Mouse Models
3. Chemotoxic Agent Mouse Models
4. Genetically Engineered Mouse Models (GEMMs)
5. Humanized Mouse Models
6. Equipment for In Vivo Tumor Monitoring
7. Conclusions and Future Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Mouse Model | Advantages | Disadvantages | Reference | |
---|---|---|---|---|
Syngeneic | • Not artificial | • Lack of diverse cancer cell line and heterogeneity | [15,17,18,19,20,21,22] | |
• Easy to utilize | • Mostly chemical induced cancer cell line | |||
• Rapid tumor development | • Tumor does not develop from normal cells or develop in a natural microenvironment | |||
• Reproducible | • Mouse and human immune systems have vital differences | |||
• Low in cost | • Might cause a vaccination effect | |||
• Tumor can be accurately monitored without difficulty | • Human HCC cannot be completely recapitulated by mouse cancer cells in terms of the complexity, histology, and natural carcinogenesis characteristics | |||
• Non-immunogenic | • Short experimental window | |||
Chemotoxic agent | • Easy to work with | • Tumor formation is not initiated by chronic inflammation | [18,19,20,21,23] | |
• Sporadic cancer development | ||||
• Higher heterogeneity | • Difficult to monitor a tumor | |||
• Tumors generally progress in a natural microenvironment and develop from normal cells | • Variability in the time for tumor progression | |||
• Available to incorporate with other approaches for tumor induction | • Larger sample sizes are needed for data interpretation due to the high heterogeneity | |||
GEMM | • Encompasses natural tumor microenvironments | • Longer latency and time for tumor development | [15,17,18,19,20,21,22] | |
• The genetic and histopathological aspects of all stages of cancer can be recapitulated | • Difficult to monitor a tumor | |||
• Low immunogenicity | ||||
• Costly and challenging for breeding and gene manipulation | ||||
• Tumors develop from normal cells | • Homogeneous in the genomic aspect | |||
Humanized | CD34+ | • Immediately available for experiment | • 4–8 weeks of experimental window | [15,21,24,25] |
• The complex human immune system and human HCC can be recapitulated | • Difficult to set up | |||
PBL | • The entire complex human immune system can be established | • 10-12 weeks are required for HSC engraftment | [15,21,24,25] | |
• Difficult to set up | ||||
• Human HCC can be recapitulated | • High in cost |
Model | Growth Site | Mice Background | Inducer | Dose | Tumor Harvest | References |
---|---|---|---|---|---|---|
CA | Orthotopic | C57BL/6 | DEN | 10~35 mg/kg/once | 8~12 months | [23,26,27,28] |
DEN+ thioacetamide | 20 mg/kg/weekly | 2 months | [29] | |||
DEN+ carbon tetrachloride | 8 mL/kg/twice a week | 6 months | [30] | |||
BALB/c | Tamoxifen | 1 mg/mice/once | 4~5 months | [31] | ||
SG | Orthotopic | C3H; C57BL/6 | HCA-1; RIL-175 | 1 × 106; 1 × 105 | No data; 3 weeks | [32,33] |
BALB/c; C57BL/6 | Hepa1 -6; BNL-1MEA | 2 × 106 | 1 week | [26,32,34] | ||
Subcutaneous | C57BL/6 | RIL-175 | 1 × 106 | 150 mm3 | [33] | |
BALB/c | BNL-1MEA | 1 × 106 | 200 mm3 | [33] | ||
GEMM | Orthotopic | C57BL/6 | Alb-cre Pten | 9 months | [26] | |
Alb-cre Shp2 | 2 months | [35] | ||||
Akt1−/−,Akt2 −/− | 5~6 months | [23] | ||||
Alb-IKKβ | 20 months | [36] | ||||
Alb-HBV | 28 weeks | [37] | ||||
BALB/c | Alb-floxStop-SV40 | 7(20) weeks | [31] | |||
C57BL/6 | P14 | [38] | ||||
HMM | Subcutaneous | NSG | Patient-derived tumor | 8~10 weeks | [39] |
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Li, E.; Lin, L.; Chen, C.-W.; Ou, D.-L. Mouse Models for Immunotherapy in Hepatocellular Carcinoma. Cancers 2019, 11, 1800. https://doi.org/10.3390/cancers11111800
Li E, Lin L, Chen C-W, Ou D-L. Mouse Models for Immunotherapy in Hepatocellular Carcinoma. Cancers. 2019; 11(11):1800. https://doi.org/10.3390/cancers11111800
Chicago/Turabian StyleLi, Enya, Li Lin, Chia-Wei Chen, and Da-Liang Ou. 2019. "Mouse Models for Immunotherapy in Hepatocellular Carcinoma" Cancers 11, no. 11: 1800. https://doi.org/10.3390/cancers11111800