Dendritic Cell Vaccines for Glioblastoma: A Systematic Review and Meta-Analysis Comparing New-Onset and Recurrent Cases.

Next-generation CAR immunotherapy for neuroblastoma: expanding the role of immune cell platforms.

Neuroblastoma (NB) is a pediatric cancer that develops from immature nerve cells in the peripheral sympathetic nervous system. NB is remarkably heterogeneous, ranging from spontaneous regression to aggressive progression, and is characterized by widespread dissemination and relapse. Approximately half of all NB patients present with widespread metastasis at diagnosis and are classified as high-risk with a substantial likelihood of treatment failure, despite receiving aggressive multimodal therapies, including surgery, chemotherapy, radiotherapy, autologous hematopoietic stem cell transplantation, and monoclonal antibody treatment. Beyond conventional multimodal approaches, immunotherapy has emerged as an essential part of cancer treatment, by boosting the immune system to recognize and eliminate tumor cells. In this review, we provide an overview of current therapeutic strategies for NB patients and summarize recent advances in the development of next-generation NB immunotherapies, highlighting their potential to improve NB management. We further discuss future directions for therapeutic improvement, and the potential limitations and challenges associated with translating these approaches into long-term benefits for NB patients.

Complement-Targeted Therapies in Glioblastoma: A Systematic Review

Background/Objectives: Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor in adults, with a median survival of approximately 15 months despite maximal multimodal therapy. The complement system plays a paradoxical dual role in GBM, mediating both antitumor immunity and immunosuppressive signaling within the tumor microenvironment, yet no systematic synthesis of complement-targeted therapeutic strategies exists. We aimed to comprehensively identify, appraise, and synthesize studies investigating complement-targeted therapies and complement-associated prognosis in GBM. Methods: Following PRISMA 2020 guidelines, we searched PubMed/MEDLINE and the Cochrane Library (CENTRAL) without date or language restrictions. Preclinical and clinical study designs were eligible. Risk of bias was assessed using SYRCLE, ROBINS-I, and study-type-specific checklists. Certainty of evidence was evaluated using GRADE. Statistical pooling was planned only for sufficiently comparable studies; clinical prognostic studies were synthesized narratively because they assessed non-equivalent constructs. Results: Forty-one studies were included, comprising 15 preclinical in vivo, 13 preclinical in vitro, 6 clinical observational, and 7 bioinformatics studies. Five preclinical survival studies entered a structured quantitative synthesis, but no pooled cross-target effect was calculated because their interventions, comparators, and reported summary measures were non-equivalent. Clinical prognostic studies evaluated either individual protein biomarkers or multigene immune-risk signatures and were not pooled. GRADE certainty was “Very Low” for both outcomes. C3b opsonization and the C5a/C5aR1 axis were among the most frequently studied targets. Conclusions: Complement modulation remains a promising biological hypothesis in GBM rather than evidence for clinical application, and certainty of evidence is very low. Methodological and mechanistic heterogeneity across complement targets underscore the need for standardized preclinical models and randomized clinical trials.

Immunotherapeutic strategies for castration-resistant prostate cancer: A systematic review of mechanisms, clinical advances and emerging approaches

Recent Locoregional CAR T-Cell Trials for the Treatment of Recurrent Glioblastoma: Implications for Neuro-Oncology Practice.

Glioblastoma remains one of the most aggressive primary brain tumors in adults, with a survival rarely exceeding 15 months despite multimodal therapy. Novel immunotherapeutic strategies, particularly chimeric antigen receptor T-cell therapy, have emerged as promising approaches to overcome the limitations of conventional treatments. This review summarizes recent early-phase clinical trials investigating locoregional chimeric antigen receptor T-cell delivery in recurrent glioblastoma and highlights key considerations for multidisciplinary neuro-oncology teams involved in this evolving therapeutic paradigm. Phase I studies of intratumoral, intracavitary, intraventricular, or combined delivery routes have demonstrated technical feasibility and safety, with most adverse events being manageable. Dual-route delivery may enhance chimeric antigen receptor T-cell distribution and produce early radiographic and clinical responses in selected patients. However, therapeutic durability remains limited by tumor heterogeneity, antigen loss, and the immunosuppressive tumor microenvironment. Multidisciplinary care teams play a critical role in catheter and reservoir placement, infusion planning, and management of neuroinflammatory toxicities. Although current findings are preliminary, ongoing optimization of target selection, dosing strategies, and combination therapies may expand treatment options for recurrent glioblastoma and further integrate immunotherapy into contemporary neuro-oncology care.

TIL Therapy in Relapsed/Refractory Neuroblastoma: A Translational Roadmap from Immunobiology to Early-Phase Trials.

Relapsed or refractory neuroblastoma (R/R NB) is one of the most challenging pediatric cancers, with long-term survival rates below 20%. Both standard chemotherapy and single-target immune cell therapies are associated with significant limitations. Chemotherapy is unable to clear minimal residual disease in the majority of cases, and engineered cell therapies lose efficacy when tumors drop the target antigen because of intratumoral heterogeneity. Thus, tumor-infiltrating lymphocyte (TIL) therapy offers an alternative approach. TILs are polyclonal and have previously engaged with the tumor, so they can recognize a broad spectrum of patient-specific antigens and are less likely to be compromised by the loss of a single antigen. Nevertheless, early efforts to evaluate TIL therapy in R/R NB have encountered important challenges. The primary obstacles include unsuccessful TIL manufacturing, immunosuppressive tumor microenvironment (TME), and defective antigen presentation due to MYCN-driven loss of MHC class I and impaired interferon signaling. These challenges necessitate novel approaches, such as antigen enrichment or MHC-independent engineering. This review summarizes the results of preclinical research over three decades, categorizing studies into three major periods with distinctive determinants of TIL therapy efficacy in NB. Key clinical studies are also summarized to inform the development, safety, and feasibility of TIL therapy in pediatric NB patients. Finally, a translational roadmap is proposed that integrates γδ TIL enrichment, cell engineering, TME modification, and biomarker-driven patient selection to guide early-phase clinical trials in R/R NB.

Recent Advances and Future Prospects in Gene Delivery Platforms for Glioblastoma: A Review.

This review discusses the most recent progress in genetic therapies for gliomas, with a focus on clinical platforms and those nearing clinical translation.