State of the art and perspectives of chimeric antigen receptor T cells cell therapy for neuroblastoma.

ABSTRACT

Neuroblastoma (NB) is a solid, neuroendocrine pediatric solid tumor with divergent clinical behavior. Patients with high-risk diseases have poor prognoses despite complex multimodal therapy, which requires the search for new therapeutic approaches. Chimeric antigen receptor T cells (CAR-T) have led to dramatic improvements in the survival of cancer patients, most notably those with hematologic malignancies. Early-phase clinical trials of CAR-T cell therapy for NB have proven safe and feasible, but limited clinical efficacy. At the same time, multiple experimental and preclinical studies have shown that the most common in clinical trials single 2nd or 3rd generation CAR structure is not sufficient for a complete response in solid tumors. Here, we review the recent advances and future perspectives associated with engineered receptors, including several antigens binding, armored CAR-T of 4th and 5th generation and CAR-T cell combination strategies with other immunotherapy. We also summarize the results and shortcomings of ongoing clinical trials of CAR-T therapy for NB.