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Review
. 2017 Oct;17(10):889-904.
doi: 10.1080/14737140.2017.1364995. Epub 2017 Aug 14.

Anti-GD2 immunotherapy for neuroblastoma

Sameer Sait  1 , Shakeel Modak  1
Affiliations
Review

Anti-GD2 immunotherapy for neuroblastoma

Sameer Sait et al. Expert Rev Anticancer Ther. 2017 Oct.

Abstract

Current therapeutic approaches for high-risk neuroblastoma (HR-NB) include high-dose chemotherapy, surgery and radiotherapy; interventions that are associated with long and short-term toxicities. Effective immunotherapy holds particular promise for improving survival and quality of life by reducing exposure to cytotoxic agents. GD2, a surface glycolipid is the most common target for immunotherapy. Areas covered: We review the status of anti-GD2 immunotherapies currently in clinical use for neuroblastomas and novel GD2-targeted strategies in preclinical development. Expert commentary: Anti-GD2 monoclonal antibodies are associated with improved survival in patients in their first remission and are increasingly being used for chemorefractory and relapsed neuroblastoma. As protein engineering technology has become more accessible, newer antibody constructs are being tested. GD2 is also being targeted by natural killer cells and T-cells. Active immunity can be elicited by anti-GD2 vaccines. The rational combination of currently available and soon-to-emerge immunotherapeutic approaches, and their integration into conventional multimodality therapies will require further investigation to optimize their use for HR-NB.

Keywords: GD2; Neuroblastoma; adoptive immunotherapy; anti-cancer vaccines; immunotherapy; monoclonal antibodies.

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Conflict of interest statement

Declaration of interests

S Modak is a paid consultant for Y-mabs Therapeutics Inc.; The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Fig 1.
Fig 1.
(A) Progression-free survival (PFS) for 169 patients with stage 4 neuroblastoma in first remission after consecutive immunotherapy regimens: 3F8 alone (regimen A-high risk [HR]; n 43), 3F8 plus intravenous granulocyte-macrophage colony- stimulating factor (GM-CSF) 13-cis-retinoic acid (CRA; regimen B-HR; n 41), and 3F8 plus subcutaneous GM-CSFCRA (regimen C-HR; n57 and regimen C-ultra HR [UHR]; n28); P.018 (derived from log-rank test to compare PFS among these four groups). (B) Overall survival (OS) among same cohort of patients; P .003 (derived from log-rank test to compare OS among these four groups). Reprinted from [4] with permission from the American Society of Clinical Oncology. All rights reserved.
Figure 2.
Figure 2.. Kaplan-Meier Estimates of Survival among the 226 study patients who had been randomly assigned, according to treatment group.
Data are shown for event-free survival (Panel A) and overall survival (Panel B) for all 226 patients and for event-free survival (Panel C) and overall survival (Panel D) for the 179 patients 1 year of age or older at enrollment. The estimated survival (+/− SE) at 2 years is indicated in each plot. Reprinted from [3] with permission from Massachusetts Medical Society.
See this image and copyright information in PMC

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