Review examines cell therapies for children’s brain tumors
Animal models showed activity against several tumor targets, while small early clinical programs produced mixed and preliminary results.
High evidenceMixed evidenceInterpret with caution
Medical disclaimer: This article summarizes research findings and is for informational purposes only. It is not medical advice.
Editorial illustration — not from the study.
Researchers systematically reviewed studies of genetically modified immune cells and other immune-cell products aimed at pediatric brain tumors. The review covered CAR-T cells, T-cell receptor-engineered T cells, natural killer cells, and gamma-delta T cells, including both preclinical studies and early clinical programs. It assessed targets such as HER2, B7-H3, GD2, IL13Rα2, EGFR806, and EphA proteins, as well as how the cells were delivered and how long they remained detectable.
In animal studies, several approaches were associated with tumor control or longer survival than control treatments. In early clinical programs, some locally delivered products were associated with tumor shrinkage, stable disease, or mostly lower-grade side effects, but these studies were small and exploratory. The review emphasizes that the results are not yet enough to determine how well these therapies work across children with brain tumors.
What the review examined
The researchers conducted a systematic review following PRISMA methods. They searched PubMed, Embase, and Scopus from database inception through September 17, 2025, limiting results to English-language reports. The review included preclinical and clinical studies of CAR-T cells, T-cell receptor-engineered T cells, natural killer cells, and gamma-delta T cells directed at selected tumor markers in pediatric brain tumors. The reviewers examined tumor and molecular features, cell engineering, treatment schedules and delivery routes, lymphodepletion, toxicities such as cytokine release syndrome and neurologic inflammatory toxicities, tumor response, survival, cell persistence, trafficking, cytokines, and changes in tumor antigens. Two reviewers independently extracted information from 34 studies.
Key conclusions
The review identified 324 records, removed 103 duplicates, screened 221 titles and abstracts, assessed 180 full texts, and extracted data from 34 studies. In vivo preclinical studies, which are generally animal studies, reported antitumor activity for HER2-targeted cells in medulloblastoma, GD2-targeted cells in diffuse midline glioma, and multi-target products involving IL13Rα2 and EphA2 in medulloblastoma and ependymoma. These animal studies reported longer survival than controls. Other preclinical findings included selective killing of medulloblastoma cells by gamma-delta T cells targeting EphA proteins and reduced diffuse intrinsic pontine glioma growth with GD2 CAR-NK-92 cells. These results are not evidence of benefit in people.
In early clinical programs involving people, delivery route appeared to affect safety and biological activity. For GD2-targeted therapy, low-dose intravenous treatment followed by repeated delivery into the brain’s fluid spaces was associated with objective radiographic regressions, while dose-limiting cytokine release syndrome was reported at higher intravenous doses. B7-H3 CAR-T cells delivered into the brain’s fluid spaces without lymphodepletion allowed repeated dosing and were mainly associated with grade 1 to 2 events in the reported studies, with persistence localized largely to cerebrospinal fluid. Weekly intracranial EGFR806 CAR-T cells were reported as feasible and tolerated in a small cohort, with stable disease as the best response. Across clinical trials, immune-cell persistence and immune activation were most apparent in cerebrospinal fluid. The review also described combination strategies that increased activity in the reported studies, but the abstract does not establish their effectiveness in routine patient care.
Who this is relevant to
These findings are most relevant to researchers and clinicians studying experimental immune-cell therapies for children with brain tumors. The clinical evidence comes from early programs and small cohorts, while some findings came from animal studies; animal results do not yet apply to patients, and the review does not establish that any approach is effective for routine care.
The significance
Pediatric brain tumors can be difficult to target because immune-cell products must reach tumors in the central nervous system while limiting harmful effects elsewhere. This review organizes evidence about which tumor markers and delivery routes are being studied and highlights cerebrospinal-fluid monitoring as an important research measure. However, the strongest signals were often from animal or other preclinical models, and the human evidence was early and limited. The findings may help guide further research, but they do not show that these approaches are effective or sufficiently established for broad clinical use.
Limitations & evidence assessment
The review included only English-language reports and searched the literature through September 17, 2025, so newer or non-English evidence may be missing. The 34 studies varied in tumor type, cell product, target, delivery route, and outcome measures, making direct comparisons difficult. Much of the evidence came from preclinical animal or laboratory models and may not translate to people. The clinical findings came from early programs and small cohorts, and the abstract does not provide enough information about follow-up duration, control groups, or the completeness of safety and survival comparisons.
Why this evidence level: Systematic review aggregating primary studies with explicit methodology.
Evidence levels are editorial estimates derived from study metadata — they are not clinical appraisals.
This review analyzed human studies comparing two treatments given before surgery for locally advanced esophageal or esophagogastric junction adenocarcinoma: FLOT chemotherapy and CROSS chemoradiotherapy. The pooled estimate favored FLOT for overall survival, but the groups had similar three-year survival, tumor response, surgical margins, and several major perioperative outcomes.
A systematic review examined whether Passiflora edulis, commonly known as passion fruit, is linked with lower blood pressure. It included six preclinical studies and two human trials; the animal and laboratory findings were generally more extensive than the human evidence. The authors reported possible blood-pressure reductions but emphasized that the human studies were small, varied in the extracts used, and short in duration.
Researchers studied 96 people with high-risk, locally advanced rectal cancer in a single-center phase II clinical trial. The treatment combined chemotherapy, short-course radiation, and a targeted drug selected for each study cohort. Overall, 40% had a complete response, but the study did not establish how this approach compares with other treatments.
