CAR T-cell therapy: a potential treatment strategy for pediatric midline gliomas.
Anand Kumar DasMainak SinhaSaraj Kumar SinghAnurag ChaudharyAshim Kumar BoroManish AgrawalSona BhardwajSimmi KishoreKatyayani KumariPublished in: Acta neurologica Belgica (2024)
Pediatric brain tumors are the primary cause of death in children with cancer. Diffuse midline glioma (DMG) and diffuse intrinsic pontine glioma (DIPG) are frequently unresectable due to their difficult access location, and 5-year survival remains less than 20%. Despite significant advances in tumor biology and genetics, treatment options remain limited and ineffective. Immunotherapy using T cells with a chimeric antigen receptor (CAR) that has been genetically engineered is quickly emerging as a new treatment option for these patients. High levels of expression were detected for both disialoganglioside (GD2) and B7-H3 in pediatric DMG/DIPG. Numerous studies have been conducted in recent years employing various generations of GD2-CAR T cells. The two most prevalent adverse effects found with this therapy are cytokine release syndrome, which varies in severity from mild constitutional symptoms to a high-grade disease associated with potentially fatal multi-organ failure, and neurotoxicity, known as CAR T-cell-related encephalopathy syndrome. During the acute phase of anticancer action, peri-tumoral neuro-inflammation might cause deadly hydrocephalus. The initial results of clinical trials show that the outcomes are not highly encouraging as B cell malignancies and myelomas. In vivo research on CAR T-cell therapy for DIPG has yielded encouraging results, but in human trials, the early results have shown potentially fatal side effects and very modest, but fleeting improvements. Solid tumors present a hindrance to CAR T-cell therapy because of the antigenic dilemma and the strong immune-suppressing tumor microenvironment.
Keyphrases
- cell therapy
- high grade
- low grade
- clinical trial
- stem cells
- mesenchymal stem cells
- end stage renal disease
- oxidative stress
- newly diagnosed
- poor prognosis
- randomized controlled trial
- papillary thyroid
- case report
- ejection fraction
- prognostic factors
- radiation therapy
- early onset
- adipose tissue
- depressive symptoms
- signaling pathway
- type diabetes
- long non coding rna
- binding protein
- metabolic syndrome
- squamous cell carcinoma
- induced pluripotent stem cells
- climate change
- weight loss
- sleep quality
- drug induced