Abstract
Neuroblastoma is one of the few childhood cancers that carries a tumor-specific antigen in the form of a glycolipid antigen known as GD2. It has restricted expression in normal tissue, such as peripheral afferent nerves. Monoclonal antibodies targeting GD2 have been applied clinically to high-risk neuroblastoma with significant success. However, there are different anti-GD2 products and administration regimens. For example, anti-GD2 has been used in combination with chemotherapy during the induction phase or with retinoic acid during the maintenance stage. Regimens also vary in the choice of whether to add cytokines (i.e., IL-2, GMCSF, or both). Furthermore, the addition of an immune enhancer, such as β-glucan, or allogeneic natural killer cells also becomes a confounder in the interpretation. The question concerning which product or method of administration is superior remains to be determined. So far, most studies agree that adding anti-GD2 to the conventional treatment protocol can achieve better short- to intermediate-term event-free and overall survival, but the long-term efficacy remains to be verified. How to improve its efficacy is another challenge. Late relapse and central nervous system metastasis have emerged as new problems. The methods to overcome the mechanisms related to immune evasion or resistance to immunotherapy represent new challenges to be resolved. The newer anti-GD2 strategies, such as bispecific antibody linking of anti-GD2 with activated T cells or chimeric antigen receptor T cells, are currently under clinical trials, and they may become promising alternatives. The use of anti-GD2/GD3 tumor vaccine is a novel and potential approach to minimizing late relapse. How to induce GD2 expression from tumor cells using the epigenetic approach is a hot topic nowadays. We expect that anti-GD2 treatment can serve as a model for the use of monoclonal antibody immunotherapy against cancers in the future.
Highlights
Immunotherapy is a novel emerging anti-cancer strategy in recent years
There are different forms of immunotherapy, and they can be categorized into groups based on their mechanism of action: (1) cytokines, such as interferon, inducing host immune response [1]; (2) monoclonal antibodies, such as anti-CD20 [2], anti-EGFR [3], anti-VEGF [4], and anti-GD2 [5], targeting tumor-specific antigens; (3) immune cellular therapy, including cytokine-induced killer (CIK) cells [6], dendritic cells (DCs) [7], natural killer (NK) cells [8], and chimeric antigen receptor T (CAR-T) cells [9]; (4) immune checkpoint inhibitors, including programmed cell death 1 (PD-1), programmed cell death ligand 1 (PDL-1), and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) inhibitors [10]; and (5) bioengineered oncolytic viruses [11] or bacteria [12]
Due to the possibility of inducing human antimouse antibody (HAMA) [35], this form of monoclonal antibody was subsequently replaced by chimeric antibody
Summary
There are different forms of immunotherapy, and they can be categorized into groups based on their mechanism of action: (1) cytokines, such as interferon, inducing host immune response [1]; (2) monoclonal antibodies, such as anti-CD20 [2], anti-EGFR [3], anti-VEGF [4], and anti-GD2 [5], targeting tumor-specific antigens; (3) immune cellular therapy, including cytokine-induced killer (CIK) cells [6], dendritic cells (DCs) [7], natural killer (NK) cells [8], and chimeric antigen receptor T (CAR-T) cells [9]; (4) immune checkpoint inhibitors, including programmed cell death 1 (PD-1), programmed cell death ligand 1 (PDL-1), and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) inhibitors [10]; and (5) bioengineered oncolytic viruses [11] or bacteria [12]. Over the past two decades, known as gangliosides [15,16] and their subsequent application have improved outcomes the discovery of monoclonal antibodies against neuroblastoma-specific surface antigens in high-risk significantly [5,17,18].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
