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Preclinical pediatric brain tumor models for immunotherapy: Hurdles and a way forward
Deepak Kumar Mishra1, Dean Popovski2, Shelli M Morris3
1Center for Childhood Cancer Research, Nationwide Children's Hospital, Columbus, Ohio, USA.
Abstract:
Brain tumors are the most common solid tumor in children and the leading cause of cancer-related deaths. Over the last few years, improvements have been made in the diagnosis and treatment of children with Central Nervous System tumors. Unfortunately, for many patients with high-grade tumors, the overall prognosis remains poor. Lower survival rates are partly attributed to the lack of efficacious therapies. The advent and success of immune checkpoint inhibitors (ICIs) in adults have sparked interest in investigating the utility of these therapies alone or in combination with other drug treatments in pediatric patients. However, to achieve improved clinical outcomes, the establishment and selection of relevant and robust preclinical pediatric high-grade brain tumor models is imperative. Here, we review the information that influenced our model selection as we embarked on an international collaborative study to test ICIs in combination with epigenetic modifying agents to enhance adaptive immunity to treat pediatric brain tumors. We also share challenges that we faced and potential solutions.
Insights
Developing effective treatments for pediatric high-grade brain tumors is crucial. This study explores using immune checkpoint inhibitors (ICIs) with epigenetic agents in preclinical models to improve outcomes for these challenging childhood cancers.
Area of Science:
- Pediatric Oncology
- Neuro-oncology
- Cancer Immunology
Background:
- High-grade brain tumors are the leading cause of cancer death in children, with poor prognoses due to limited effective therapies.
- Immune checkpoint inhibitors (ICIs) show promise, but their efficacy in pediatric brain tumors requires further investigation.
- Robust preclinical models are essential for testing novel therapeutic strategies in pediatric high-grade brain tumors.
Approach:
- This review details the selection of preclinical models for an international collaborative study.
- The study investigates combining immune checkpoint inhibitors (ICIs) with epigenetic modifying agents.
- The goal is to enhance adaptive immunity against pediatric brain tumors.
Key Points:
- Establishing relevant preclinical models is critical for advancing pediatric brain tumor research.
- Combination therapy with ICIs and epigenetic agents may improve treatment outcomes.
- Addressing challenges in model selection and implementation is key to successful clinical translation.
Conclusions:
- Further research into novel therapeutic combinations is needed for pediatric high-grade brain tumors.
- Preclinical models play a vital role in evaluating the potential of immunotherapies like ICIs.
- International collaboration and careful model selection can accelerate the development of better treatments for childhood brain cancers.
