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The safety and efficacy of GD2-targeted CAR-T cells in patients with neuroblastoma: a systematic review and
Mohammad Amin Habibi1, Ali Zand2, Behrouz Robat-Jazi3
1Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Objectives:
Neuroblastoma (NB) is a common and life-threatening pediatric solid tumor with a poor prognosis, especially in high-risk patients. Although anti-disialoganglioside GD2 (GD2) monoclonal antibodies improve survival, relapse and resistance remain major challenges. This study aimed to evaluate the safety and efficacy of GD2-targeted chimeric antigen receptor (CAR)-T-cell therapy in NB patients.
Methods:
A literature search was conducted in PubMed, Embase, Scopus, and Web of Science until September 30, 2025. Eligible studies were clinical trials that evaluated the efficacy and safety of GD2-targeted CAR-T-cell therapy in NB patients. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. The random-effects meta-analysis model was used to calculate pooled amounts.
Results:
Eight studies that included 146 patients with NB were included. The pooled complete response (CR) rate was 39.57% (21.17-57.96), and the partial response (PR) rate was 15.83% (5.02-30.45). Additionally, the rates of progressive disease (PD) and stable disease (SD) were 20.9% (3.06-46.67) and 30.76% (12.81-51.91), respectively. The most common "any grade" adverse events (AEs) was anemia, at 97.43% (81.51-100), and the most common "grade ≥ 3" AEs was neutropenia, at 93.46% (72.65-100). Subgroup analyses revealed that CAR-T-cell generation and its components influenced efficacy and safety.
Conclusion:
CAR-T-cell therapy targeting the GD2 antigen is promising for treating NB. However, its efficacy is moderate, and treatment can lead to hematologic toxicities such as anemia, neutropenia, and thrombocytopenia, which require careful monitoring.
Insights
Chimeric antigen receptor (CAR)-T-cell therapy targeting disialoganglioside GD2 shows promise for neuroblastoma (NB) treatment. While effective, this therapy has moderate efficacy and can cause hematologic toxicities requiring close monitoring.
Area of Science:
- Pediatric Oncology
- Immunotherapy
- Cancer Treatment
Background:
- Neuroblastoma (NB) is a significant pediatric cancer with poor prognosis, particularly in high-risk cases.
- Current treatments, including anti-GD2 monoclonal antibodies, face challenges with relapse and resistance.
- GD2-targeted therapies offer a potential avenue for improving patient outcomes.
Purpose of the Study:
- To evaluate the safety and efficacy of GD2-targeted chimeric antigen receptor (CAR)-T-cell therapy in neuroblastoma patients.
- To synthesize current evidence on CAR-T-cell therapy for NB through a meta-analysis.
Main Methods:
- A comprehensive literature search was performed across major databases (PubMed, Embase, Scopus, Web of Science) until September 2025.
- Eligible studies included clinical trials assessing GD2-targeted CAR-T-cell therapy in NB.
- Data were extracted and analyzed using a random-effects meta-analysis model.
Main Results:
- Eight studies involving 146 NB patients were analyzed.
- Pooled response rates included 39.57% complete response (CR) and 15.83% partial response (PR).
- Common adverse events (AEs) were anemia (97.43%) and neutropenia (93.46% for grade ≥3).
Conclusions:
- GD2-targeted CAR-T-cell therapy presents a promising treatment option for neuroblastoma.
- The therapy demonstrates moderate efficacy but is associated with significant hematologic toxicities.
- Close monitoring for adverse events like anemia, neutropenia, and thrombocytopenia is crucial.
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