New Era of Immunotherapy in Pediatric Brain Tumors: Chimeric Antigen Receptor T-Cell Therapy.

Immunotherapy, including chimeric antigen receptor (CAR) T-cell therapy, immune checkpoint inhibitors, cancer vaccines, and dendritic cell therapy, has been incorporated as a fifth modality of modern cancer care, along with surgery, radiation, chemotherapy, and target therapy. Among them, CAR T-cell therapy emerges as one of the most promising treatments. In 2017, the first two CAR T-cell drugs, tisagenlecleucel and axicabtagene ciloleucel for B-cell acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL), respectively, were approved by the Food and Drug Administration (FDA). In addition to the successful applications to hematological malignancies, CAR T-cell therapy has been investigated to potentially treat solid tumors, including pediatric brain tumor, which serves as the leading cause of cancer-associated death for children and adolescents. However, the employment of CAR T-cell therapy in pediatric brain tumors still faces multiple challenges, such as CAR T-cell transportation and expansion through the blood-brain barrier, and identification of the specific target antigen on the tumor surface and immunosuppressive tumor microenvironment. Nevertheless, encouraging outcomes in both clinical and preclinical trials are coming to light. In this article, we outline the current propitious progress and discuss the obstacles needed to be overcome in order to unveil a new era of treatment in pediatric brain tumors.

Viral etiologies of acute respiratory tract infections among hospitalized children - A comparison between single and multiple viral infections.

BACKGROUND: Acute respiratory tract infections are commonly caused by viruses in children. The differences in clinical data and outcome between single and multiple viral infections in hospitalized children were analyzed. METHODS: We retrospectively reviewed the medical records of hospitalized children who had fever and a xTAG Respiratory Virus Panel (RVP) test over a 2-year period. The clinical data were analyzed and compared between single and multiple viral infections. Viral etiologies in upper and lower respiratory infections were analyzed and compared. RESULTS: A total of 442 patients were enrolled. Patients with positive viral detection (N = 311) had a significantly lower rate of leukocytosis (p = 0.03), less evidence of bacterial infection (p = 0.004), and shorter duration of hospitalization (p = 0.019) than those with negative viral detection. The age of patients with multiple viral infections was younger than those with single viral infection; however, there were no significant differences in duration of fever, antibiotics treatment and hospitalization between these two groups. The most commonly identified virus was human rhinovirus. About 27% (n = 83) of patients had multiple viral infections. Overall, the highest percentage of human bocavirus infection was detected in multiple viral infections (79%). Lower respiratory tract infection (LRTI) was independently associated with multiple viral infections (p = 0.022), respiratory syncytial virus (RSV) infection (p = 0.001) and longer hospitalization duration (p = 0.011). CONCLUSION: Multiple viral infections were associated with younger age and a higher risk of developing LRTI. However, multiple viral infections did not predict a worse disease outcome. More studies are needed to unveil the interplay between the hosts and different viruses in multiple viral infections.