title: Advances in chimeric antigen receptor immunotherapy for neuroblastoma.
abstract: Neuroblastoma (NBL) is the most common extracranial pediatric solid tumor and has heterogeneous biology and behavior. Patients with high-risk disease have poor prognosis despite complex multimodal therapy; therefore, novel curative approaches are needed. Immunotherapy is a novel therapeutic approach that harnesses the inherent activity of the immune system to control and eliminate malignant cells. One form of immunotherapy uses chimeric antigen receptors (CAR) to target tumor-associated antigens. CARs are derived from the antigen-binding domain of a monoclonal antibody (MAb) coupled with the intracellular signaling portion of the T cell receptor. CARs can combine the specificity and effectiveness of MAbs with the active bio-distribution, direct cytotoxicity, and long-term persistence of T cells. NBL provides an attractive target for CAR immunotherapy as many of its tumor-associated antigens are not expressed at significant levels on normal tissues, thus decreasing potential treatment related toxicity. Two previous clinical trials utilizing L1-cell adhesion molecule (L1-CAM) and disialoganglioside (GD2) specific CARs (GD2-CAR) have demonstrated safety and anti-tumor efficacy in heavily pretreated relapsed/refractory neuroblastoma patients. Based on these promising results and on improved techniques that can further potentiate CAR therapies, two clinical trials are currently investigating the use of GD2-CARs in children with NBL. Several approaches may further enhance anti-tumor activity and persistence of CAR modified cells, and if these can be safely translated into the clinic, CAR-based immunotherapy could become a viable adjunct or potential alternative to conventional treatment options for patients with NBL.
authors: Department of Pediatrics and Center for Cell and Gene Therapy, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Andras
authors: A
authors: Heczey
authors: Chrystal U
authors: CU
authors: Louis
mesh_terms: D019264:Adoptive Transfer; D000911:Antibodies, Monoclonal / Q000737:chemistry; D002648:Child; D002986:Clinical Trials as Topic; D019672:Genes, T-Cell Receptor / Q000235:genetics; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation; D009447:Neuroblastoma / Q000276:immunology* / Q000628:therapy*; D011379:Prognosis; D011946:Receptors, Antigen / Q000737:chemistry*; D012306:Risk
chemical_list: D000911:Antibodies, Monoclonal; D011946:Receptors, Antigen