Immunotherapeutic Strategies for Neuroblastoma: Present, Past and Future

Abstract

Neuroblastoma is the most common extracranial pediatric solid tumor with a heterogeneous clinical course, ranging from spontaneous regression to metastatic disease and death, irrespective of intensive chemotherapeutic regimen. On the basis of several parameters, children affected by neuroblastoma are stratified into low, intermediate and high risk. At present, more than 50% of high-risk patients with metastatic spread display an overall poor long-term outcome also complicated by devastating long-term morbidities. Thus, novel and more effective therapies are desperately needed to improve lifespan of high-risk patients. In this regard, adoptive cell therapy holds great promise and several clinical trials are ongoing, demonstrating safety and tolerability, with no toxicities. Starting from the immunological and clinical features of neuroblastoma, we here discuss the immunotherapeutic approaches currently adopted for high-risk patients and different innovative therapeutic strategies currently under investigation. The latter are based on the infusion of natural killer (NK) cells, as support of consolidation therapy in addition to standard treatments, or chimeric antigen receptor (CAR) T cells directed against neuroblastoma associated antigens (e.g., disialoganglioside GD2). Finally, future perspectives of adoptive cell therapies represented by γδ T lymphocyes and CAR NK cells are envisaged.

Impact of 11q Loss of Heterozygosity Status on the Response of High-Risk Neuroblastoma With MYCN Amplification to Neoadjuvant Chemotherapy

“…Patients were grouped and staged according to the INRG classification and staging system (19,20). The clinical stage of the patients was confirmed by fluorodeoxyglucose positron emission tomography, computerized tomography and/or metaiodobenzylguanidine (MIBG) scan in addition to other methods such as bone marrow biopsy, bone scan, cranial magnetic resonance imaging and ultrasonic examination (18).…”

Immunotherapies for Pediatric Solid Tumors: A Targeted Update

“…A recent update from a phase III trial (HR-NBL1/SIOPEN) demonstrated no additional benefit and added toxicity with interleukin (IL)-2 when given with dinutuximab to patients with high-risk neuroblastoma [19], leading to discontinuation of use of IL-2 in similar COG protocols. Other recent advances with anti-GD2 antibodies in neuroblastoma are reviewed elsewhere [20].…”

Dinutuximab beta in the treatment of high-risk neuroblastoma

“…In recent years, harnessing the body's own immune system via immunotherapies has proven to be an effective strategy in many cancer types, [ 3 ] and addition of immunotherapy agents to existing cytotoxic regimens has demonstrated improved outcomes for patients with neuroblastoma. [ 3 – 6 ]…”