Literature review: CAR T-cell therapy as a promising immunotherapeutic approach for medulloblastoma

Abstract

Medulloblastoma (MB) accounts for approximately 20–25% of all childhood brain tumours and 63% of intracranial embryonic tumours, with an annual incidence of around 5 cases per million in the paediatric population. This high-grade neuroepithelial tumour of the posterior fossa can develop at any age during childhood, adolescence and even adulthood, often spreading via cerebrospinal fluid. While most MB cases are sporadic, they can be associated with genetic predisposition syndromes. Although these genetic mutations present potential therapeutic targets, the limited number of mutations and few existing therapies aimed at these neoantigens pose significant challenges. Despite aggressive multimodal treatment approaches, approximately 30% of patients ultimately succumb to MB, and survivors frequently face long-term side effects that severely impact their quality of life. MB harbours unique molecular factors, necessitating careful consideration of therapeutic targets such as the blood-brain barrier, tumour microenvironment, and the differing responses of cancer stem cells versus bulk tumour tissue. Conventional treatment typically involves maximal safe resection, risk-adapted chemotherapy, and/or radiation craniospinal irradiation. While there is general agreement on the benefits of chemotherapy for MB patients, adverse side effects remain prevalent, underscoring the need for alternative therapeutic strategies. Given the heterogeneous nature of MBs and the lack of salvage treatment, immunotherapy has emerged as a promising novel treatment avenue. This personalized approach aims to enhance specificity and potentially reduce side effects. Among these innovative methods, adoptive cell therapy, particularly chimeric antigen receptor T (CAR T) cell therapy, shows great promise. This review will explore the potential of CAR T-cell therapies in targeting MB, building on their successful application in other solid tumours.