Various applications of stem-cell-targeted radioimmunotherapy for the treatment of cancer: A narrative review.

[BACKGROUND AND PURPOSE] Cancer stem cells (CSCs) drive tumor relapse and resist conventional therapies. Radioimmunotherapy (RIT) combines monoclonal antibodies with radionuclides to deliver cytotoxic radiation. Targeting CSCs or using stem cells as delivery vehicles may enhance efficacy.

[MATERIALS AND METHODS] A narrative review was conducted using Google Scholar, Web of Science, Scopus, and PubMed to identify original studies on CSC-targeted RIT, engineered stem cells, and stem cell rescue to support myeloablative RIT. Data on radionuclide constructs, stem cell platforms, cancer models, and outcomes were synthesized and compiled.

[RESULTS] α- and β-emitters effectively ablated CSCs in hematologic and solid tumor murine models, resulting in CSC depletion, reduced tumor volume, and delayed tumor progression. MSCs engineered to express NIS under tumor-responsive promoters (hypoxia, TGFB1, CMV) enabled selective uptake of ^123I and ^131I. In xenograft models of hepatocellular carcinoma, glioblastoma, and breast cancer, this approach permitted noninvasive imaging and significant tumor growth inhibition. Myeloablative RIT regimens paired with autologous or allogeneic HSC transplantation allowed dose escalation in hematologic malignancies and metastatic bone disease. Hematopoietic recovery was consistently achieved without impairing engraftment.

[CONCLUSIONS] Stem-cell-targeted RIT integrates direct CSC eradication, MSC-mediated radionuclide delivery, and HSC support to maximize antitumor efficacy. Key challenges remain, including CSC antigen heterogeneity, off-target radiation to normal tissues, dosimetry optimization, and logistical constraints associated with radionuclide handling and cell sourcing. Future efforts should focus on multi-antigen targeting strategies, nonviral gene delivery platforms, advanced imaging-guided dosimetry, and early translational studies to validate safety and efficacy in clinical settings.