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Immune Checkpoint Blockade Biology in Mouse Models of Glioblastoma
Alan T Yeo1,2, Alain Charest2,3
1Sackler School of Graduate Studies, Tufts University School of Medicine, 136 Harrison Ave, Boston, Massachusetts 02111.
Abstract:
Glioblastoma Multiforme (GBM) is a highly malignant primary brain cancer that is associated with abysmal prognosis. The median survival of GBM patients is ∼15 months and there have not been any significant advance in therapies in over a decade, leaving treatment options limited. There is clearly an unmet need for GBM treatment. Immunotherapies are treatments based on usurping the power of the host's immune system to recognize and eliminate cancer cells. They have recently proven to be a successful strategy for combating a variety of cancers. Of the various types of immunotherapies, checkpoint blockade approaches have thus far produced significant clinical responses in several cancers including melanoma, non small-cell lung cancer, renal cancer, and prostate cancer. This review focuses on the biological rationale for using checkpoint blockade immunotherapeutic approaches in primary brain cancer and an up-to-date summary of current and ongoing checkpoint inhibitors-based clinical trials for malignant glioma. In addition, we expand on new concepts for further improving checkpoint blockade treatments, with a particular focus on the advantages of using genetically engineered mouse models for studies of immunotherapies in GBM. J. Cell. Biochem. 118: 2516-2527, 2017. © 2017 Wiley Periodicals, Inc.
Insights
Checkpoint blockade immunotherapies show promise for treating glioblastoma multiforme (GBM), a deadly brain cancer. This review explores the rationale and clinical trials for using these immune-boosting strategies in GBM treatment.
Area of Science:
- Neuro-oncology
- Immunotherapy
- Cancer Research
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain cancer with limited treatment options and poor prognosis.
- Current therapies for GBM have seen minimal advancements in over a decade, highlighting an unmet clinical need.
- Immunotherapies, particularly checkpoint blockade, have shown success in treating various cancers by harnessing the immune system.
Purpose of the Study:
- To review the biological basis for applying checkpoint blockade immunotherapies to primary brain tumors.
- To summarize current and ongoing clinical trials of checkpoint inhibitors for malignant glioma.
- To discuss novel strategies for enhancing checkpoint blockade efficacy in GBM, including the use of genetically engineered mouse models.
Main Methods:
- Literature review of immunotherapy principles and checkpoint blockade mechanisms.
- Analysis of clinical trial data for checkpoint inhibitors in malignant glioma.
- Exploration of preclinical research, focusing on genetically engineered mouse models for GBM immunotherapy studies.
Main Results:
- Checkpoint blockade represents a promising therapeutic avenue for GBM, with ongoing clinical investigations.
- Genetically engineered mouse models offer valuable platforms for studying GBM immunotherapies.
- Further research is needed to optimize checkpoint blockade strategies for improved GBM patient outcomes.
Conclusions:
- Checkpoint blockade immunotherapy holds significant potential for improving outcomes in glioblastoma multiforme.
- The development and application of genetically engineered mouse models are crucial for advancing GBM immunotherapy research.
- Continued clinical trials and innovative therapeutic strategies are essential to overcome the challenges in treating malignant glioma.
