Tolan DA, Ebrahim NAA, AlAli NS, Ahmed HA, Alharshan GA, Arafat AMA. Stem cell-derived immune cells in pediatric cancer therapy: From bench to bedside. World J Stem Cells 2026; 18(6): 118674 [DOI: 10.4252/wjsc.118674]
Corresponding Author of This Article
Noura A A Ebrahim, Assistant Professor, Department of Oncologic Pathology, National Cancer Institute, Cairo University, 1st Kasr Alainy Street, Cairo 11796, Al Qāhirah, Egypt. npathologist@gmail.com
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Biology
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review-article
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Tolan DA, Ebrahim NAA, AlAli NS, Ahmed HA, Alharshan GA, Arafat AMA. Stem cell-derived immune cells in pediatric cancer therapy: From bench to bedside. World J Stem Cells 2026; 18(6): 118674 [DOI: 10.4252/wjsc.118674]
World J Stem Cells. Jun 26, 2026; 18(6): 118674 Published online Jun 26, 2026. doi: 10.4252/wjsc.118674
Stem cell-derived immune cells in pediatric cancer therapy: From bench to bedside
Dina A Tolan, Noura A A Ebrahim, Naif S AlAli, Hoda A Ahmed, Gharam A Alharshan, Aya Mohamed Adel Arafat
Dina A Tolan, Department of Chemistry, College of Science and Humanities, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia
Noura A A Ebrahim, Department of Oncologic Pathology, National Cancer Institute, Cairo University, Cairo 11796, Al Qāhirah, Egypt
Naif S AlAli, Family Medicine Academy, Eastern Health Cluster, Dammam 11942, Saudi Arabia
Hoda A Ahmed, Department of Chemistry, College of Science in Yanbu, Taibah University, Yanbu Governorate, Yanbu 46423, Saudi Arabia
Gharam A Alharshan, Physics Department, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia
Aya Mohamed Adel Arafat, Department of Clinical and Chemical Pathology, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo 11562, Egypt
Author contributions: Tolan DA, Ebrahim NAA, AlAli NS, Ahmed HA, Alharshan GA, and Arafat AMA contributed equally to the conceptualization, drafting, and critical revision of this manuscript.
AI contribution statement: We would like to clarify that we used Grammarly and QuillBot only as language-editing tools to improve grammar, clarity, readability, and stylistic consistency of the manuscript. Their use was limited to linguistic polishing and did not involve generation of the scientific content.
Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.
Corresponding author: Noura A A Ebrahim, Assistant Professor, Department of Oncologic Pathology, National Cancer Institute, Cairo University, 1st Kasr Alainy Street, Cairo 11796, Al Qāhirah, Egypt. npathologist@gmail.com
Received: January 8, 2026 Revised: January 30, 2026 Accepted: March 23, 2026 Published online: June 26, 2026 Processing time: 168 Days and 16.8 Hours
Abstract
Immune effector cells generated from stem cell sources, most notably induced pluripotent stem cells and hematopoietic stem cells (HSCs) differentiated into natural killer cells, T lymphocytes, and dendritic cells, represent a rapidly advancing category of off-the-shelf immunotherapies for pediatric cancers. In contrast to autologous chimeric antigen receptor-T-cell products, stem cell-based platforms enable the use of standardized, clonally controlled starting materials, support complex and multiplex genetic modifications, and facilitate scalable manufacturing processes that may substantially reduce production time and batch-to-batch heterogeneity. However, HSC-derived immune cells may preserve aspects of physiological immune maturation that enhance persistence and functional durability in vivo. Accumulating preclinical and early-phase clinical evidence has demonstrated potent antitumor activity against pediatric hematologic malignancies and select solid tumors, alongside encouraging safety profiles characterized by minimal graft-vs-host disease and reduced severe neurotoxicity, as well as compatibility with cryopreserved delivery. Nonetheless, key translational challenges remain unresolved, including the absence of robust head-to-head comparisons between induced pluripotent stem cell-derived and HSC-derived products; limited cost-effectiveness analyses relative to established therapies; and unresolved manufacturing constraints related to genomic stability, differentiation reproducibility, and potency assessment. Systematic comparative studies, transparent health-economic modeling, and rational engineering strategies emphasizing genomic monitoring, immune evasion control, and programmable safety mechanisms will be critical for defining the most appropriate clinical applications of stem cell-derived immunotherapies in pediatric oncology.
Core Tip: Immune cells generated from pluripotent or hematopoietic stem cell sources -particularly natural killer cells, T lymphocytes, and dendritic cells - represent a promising next-generation platform for pediatric cancer immunotherapy. These systems enable standardized, renewable production and genetic optimization, offering an allogeneic alternative to patient-specific cellular products with lower graft-vs-host disease risk. Advances in cytokine modulation and genome editing technologies, including CRISPR/Cas9, have further strengthened antitumor efficacy. This review critically consolidates current preclinical and early-phase clinical findings; addresses manufacturing, safety, and pediatric ethical considerations; and defines strategic directions for clinical translation.
