Immunotherapy approaches targeting neuroblastoma

Abstract

Purpose of review: In the era of immune-oncology, a breakthrough in the field of pediatric solid tumor research has been the demonstration that immunotherapy for patients with high-risk neuroblastoma improves the event-free and overall survival. Immunotherapeutic approaches including a monoclonal antibody targeting the cell surface glycosphingolipid disialoganglioside and cytokines successfully eliminate minimal residual disease.

Recent findings: Since this seminal discovery, clinical trials evaluating immunotherapy in combination with chemotherapy and cellular therapies have begun to demonstrate effectiveness in treatment of bulky disease. Broader knowledge has also been gained regarding immunotherapy-limiting side-effects. Furthermore, biologic studies in actively treated patients have contributed to our growing understanding of the underlying immunologic processes and mechanisms of tumor response and immune evasion.

Summary: The example of neuroblastoma is beginning to demonstrate that various immunotherapies combined with more conventional anticancer treatments can be synergistic. These advancements pose new challenges to both clinical researchers and medical provider and herald a new era in pediatric cancer therapy.

Figure 1:

Therapy regimen of patients with high-risk neuroblastoma. Patients undergo different phases of therapy starting with induction chemotherapy (1). Surgery is performed during induction. Consolidation therapy (2) consists of tandem transplant (BMT). Patients undergo radiation therapy to the primary tumor bed after consolidation therapy to prevent local tumor recurrence (3) and maintenance therapy in the end (4).

Figure 2:

Immunotherapy approaches to target neuroblastoma. (1) Monoclonal antibodies can either target cancer antigens or serve as self-antigens (i.e., as idiotype antibody that can be bound by the variable region of other antibodies or by T or B cell receptors). (2) The administration of exogenous cytokines can directly influence the immune or cancer cells. (3) Adoptive cells are collected from a donor or the patient, can be manipulated ex vivo, and are infused back into the patient. (4) Vaccine strategies can either provide a cancer antigen to induce immunogenicity or alter the immunologic equilibrium through the release of cytokines such as GM-CSF with the GVAX vaccine. (5) Immune-modulatory drugs have a direct or indirect impact on the endogenous immune cells.