Table 1.
Summary of GBM Model Advantages and Disadvantages
| Mouse Model | Originating Species | Uses in preclinical studies | Pros | Cons | Comments |
|---|---|---|---|---|---|
| GL261 | Mouse | - Gene therapy, immune cell transfer, monoclonal antibodies, and cytokine therapies.13,14 - Checkpoint inhibitors.15 - Dendritic cell vaccines.16,17 - Investigate GSCs.14,18 |
- Can be used in immunocompetent mice. - Widely used and available. |
- Highly immunogenic relative to human GBM - Underlying genetics are different than human GBM.19 - Homogeneous population of cells. - Significant variability between studies. |
|
| SMA-560 | Mouse | - Cytokine therapies.20 - Soluble CD70.21 - CAR T cells.22 |
- Can be used in immunocompetent mice. - Resistant to TMZ. - Secretes TGF-B, can be used to study immunosuppression in GBM.23 - Spontaneous tumor, not chemically induced. |
- Immunogenic relative to human GBM. - Less commonly used. - Not as well characterized as other models. - Homogeneous population of cells. |
|
| CT-2A | Mouse | - Evaluation of GSCs.24 - Immunotoxin against EGFRvIII.25 |
- Can be used in immunocompetent mice. - Can be used to study GSCs. |
- Tumor mutational burden not well characterized. - Likely more immunogenic than human GBM. - Moderately utilized in the literature - Low invasion into surrounding brain parenchyma.26 - Homogeneous population of cells |
- Increased immune suppression and aggressiveness when grown as neurospheres.24 |
| SB28 | Mouse | - Checkpoint inhibitors.12 - Anti-CD40 treatment.27 |
- Can be used in immunocompetent mice. - Poorly immunogenic, most closely represents tumor microenvironment of human GBM amongst syngenic models. |
- Used in less than 15 publications to date, requires additional histologic and microenvironment characterization. - Homogeneous population of cells |
|
| U251 | Human | - Alkylating agents: temozolomide, lomustine, and carmustine as well as the anti-angiogenic small molecule drug cilengitide.28 - Bevacizumab.28 - Synergism between metformin and temozolomide.29 |
- Extensively used in over 1000 studies.30,31 - Histologically recapitulates GBM well.32–35 |
- Questions regarding authenticity and inter-lab variability.32,36 - Requires the use of immunodeficient mice. - Sensitive to TMZ and XRT- does not recapitulate human GBM response to treatment. - Lack intra-tumoral heterogeneity. |
|
| U87 | Human | - Anti-angiogenic therapies.37 - Siroliumus and chloroquine in combination with temozolamide.38 - Neural stem cells carrying tumoricidal gene products.39 |
- Used in over 2000 studies.30 - Genetically similar to human GBM—carries hTERT, PTEN, and ATRX mutations.40,41 |
- Histologically, tumors are not invasive.32,33,42 - Lack other histologic characteristics of human GBM as well.32,33,35,42 - Questions regarding authenticity, inter-lab variability.43 - Requires immunodeficient mouse. - Lack intra-tumoral heterogeneity. |
|
| GEMMs | Mouse | - Used in a variety of studies investigating treatments and underlying molecular pathways of GBM.42,44,45 - TMZ treatment response.46 - Response to Hsp90 inbibitor.47 - Response to PARP inhibitor.48 |
- Can directly investigate impact of underlying tumor genetics on treatment response.46–50 - Does not require intracranial injection. - Develop more similarly to human GBM.30 |
- Lack intra-tumoral heterogeneity.28,30,44 - Can require sophisticated breeding strategies. - Can be slow to form or inconsistent. - Can be expensive - Tumor formation is variable, limiting the use of precise treatment delivery modalities. |
|
| PDX | Human | - GSCs and response to treatment.51,52 - Pharmaceuticals: bevacizumab, TMZ, veliparib.53–55 - Oncolytic herpes virus. - High-throughput drug screens. |
- Best recapitulates human GBM histology and heterogeneity.51,56 - Intra-tumoral heterogeneity. |
- Variability between lines. - Usually requires immunodeficient mouse. - Can be difficult to establish, requires significant expertise.57,58 |