Innovative ADC and CAR-T Therapies for High-Risk Neuroblastoma: A New Hope

Neuroblastoma (NB) is the most prevalent solid tumor in children, originating primarily in the adrenal gland or the extra-adrenal sympathetic chain, including regions such as the retroperitoneum, chest, and neck. The prognosis for NB varies significantly based on risk classification, with high-risk patients facing a particularly challenging outlook. Traditional treatments for high-risk and recurrent NB include a combination of chemotherapy, surgery, radiation, stem cell transplant, immunotherapy, and retinoid therapy, administered in phases of induction, consolidation, and maintenance. Despite these efforts, the efficacy of conventional treatments remains limited, especially for high-risk cases. Currently, targeted therapies are restricted to ALK inhibitors, anti-Aurora A kinase pathway drugs, and a monoclonal antibody targeting GD2. This highlights a critical need for innovative therapies. Antibody-Drug Conjugates (ADCs) and Chimeric Antigen Receptor (CAR) T-cell therapies represent promising advancements. ADCs leverage tumor-targeting antibodies to deliver toxic agents directly to cancer cells, while CAR-T cells, modified ex-vivo, offer a personalized approach by targeting specific tumor cells. Although CAR-T therapy has shown success in hematological malignancies, its potential in solid tumors like neuroblastoma is still under investigation. Recent studies have demonstrated the effectiveness of GD2-, ALK-, LGALS3BP-, and GPC2-targeting ADCs, as well as anti-GD2 and anti-CD171/L1-CAM CAR-T therapies in preclinical and clinical settings.

This research topic aims to explore new advances in therapeutic approaches involving ADCs and CAR-T cell therapy, as well as the refinement and optimization of existing immunotherapeutic strategies in neuroblastoma therapy. The objective is to address novel ADC- and CAR-T-based anti-tumoral therapeutic strategies, providing insights into their potential to improve outcomes for high-risk neuroblastoma patients. Researchers are encouraged to contribute original research articles, reviews, brief research reports, case reports, clinical trials, and perspectives that delve into these innovative therapies.

To gather further insights in the realm of neuroblastoma therapy, we welcome articles addressing, but not limited to, the following themes:
- Development and optimization of ADCs targeting neuroblastoma-specific antigens.
- Advances in CAR-T cell engineering for enhanced efficacy against neuroblastoma.
- Clinical trials and case studies evaluating ADC and CAR-T therapies in neuroblastoma.
- Mechanisms of resistance to ADC and CAR-T therapies in neuroblastoma.
- Combination strategies involving ADCs, CAR-T cells, and other therapeutic modalities.
- Safety and efficacy assessments of ADC and CAR-T therapies in pediatric populations.
- Biomarker discovery for predicting response to ADC and CAR-T therapies in neuroblastoma.

Keywords: neuroblastoma, Therapy, Cell-Based, ADC, CAR-T

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.