ABSTRACT
BACKGROUND: Immune-mediated therapies have transformed the treatment of metastatic melanoma and renal, bladder, and both small and non-small cell lung carcinomas. However, immunotherapy is yet to demonstrate dramatic results in brain tumors like medulloblastoma for a variety of reasons. Recent pre-clinical and early phase human trials provide encouraging results that may overcome the challenges of central nervous system (CNS) tumors, which include the intrinsic immunosuppressive properties of these cancers, a lack of antigen targets, antigenic variability, and the immune-restrictive site of the CNS. These studies highlight the growing potential of immunotherapy to treat patients with medulloblastoma, a disease that is a frequent cause of morbidity and mortality to children and young adults. METHODS: We conducted an inclusive review of the PubMed-indexed literature and studies listed in clinicaltrials.gov using combinations of the keywords medulloblastoma, immunotherapy, CNS tumors, brain tumors, vaccines, oncolytic virus, natural killer, and CAR T to identify trials evaluating immunotherapy in preclinical experiments or in patients with medulloblastoma. Given a limited number of investigations using immunotherapy to treat patients with medulloblastoma, 24 studies were selected for final analysis and manuscript citation. RESULTS: This review presents results from pre-clinical studies in medulloblastoma cell lines, animal models, and the limited trials involving human patients. CONCLUSION: From our review, we suggest that cancer vaccines, oncolytic viral therapy, natural killer cells, and CAR T therapy hold promise against the innate immunosuppressive properties of medulloblastoma in order to prolong survival. There is an unmet need for immunotherapy regimens that target overexpressed antigens in medulloblastoma tumors. We advocate for more combination treatment clinical trials using conventional surgical and radiochemotherapy approaches in the near-term clinical development.
ABSTRACT
BACKGROUND: Checkpoint inhibitors have transformed the treatment of cancer in adults. This class of drugs has demonstrated encouraging results in various malignancies such as metastatic melanoma, bladder cancer, renal cancer, and non-small cell lung carcinoma. However, researchers have only begun investigating the effectiveness and tolerability of checkpoint inhibitors in pediatric patients. METHODS: We conducted a review of PubMed indexed literature and clinicaltrials.gov using combinations of the keywords checkpoint, inhibitor, pediatric, CTLA-4 (cytotoxic T lymphocyte antigen-4), PD-1 (programmed cell death-1), and PD-L1 (programmed cell death receptor-1 ligand) to find every recently completed and ongoing trial evaluating checkpoint inhibitors in patients younger than 21 years old. Pertinent articles and clinical trials discussing the role of immune checkpoint inhibitors in the pediatric population were selected for final analysis and manuscript citation. RESULTS: This review presents an overview of the cellular mechanisms involved in checkpoint inhibition and of studies evaluating checkpoint inhibitors in humans. The review also details results and side effects from studies conducted with pediatric patients, current pediatric clinical trials, and future implications. CONCLUSION: Immune checkpoint inhibitors have the potential to further therapeutic advances in pediatric oncology; however, we need more clinical trials and combination drug strategies targeted toward pediatric cancers.
