Dendritic Cell-Based Cancer Immunotherapy Targeting Wilms’ Tumor 1 for Pediatric Cancer
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ABSTRACT
The treatment of advanced pediatric cancers that have metastasized to distant organs remains difficult. Investigations evaluating the potential treatment of these cancers using therapeutic vaccination with an active dendritic cell (DC)-based immunotherapy are also being conducted. This method induces an efficient immune response by the acquired immune system against tumor-associated antigens. Cancer vaccination therapies have been prepared using autologous monocyte-derived mature DCs exposed to granulocyte–macrophage colony-stimulating factor and interleukin-4, which are the molecules principally attributed to the presence of tumor-associated antigens. Wilms’ tumor 1 (WT1), an attractive target antigen that has been widely detected in cancers including sarcoma and leukemia, has been shown to be the most potent tumor-associated antigen. DC-based immunotherapy targeting WT1 may have a potentially strong therapeutic activity against cancers. DC vaccines primed with human leukocyte antigen (HLA) class I-/II-restricted WT1 peptides (WT1-DC) are a feasible option. A 6-year-old girl with neuroblastoma and a 14-year-old girl with WT received autologous DC vaccination pulsed with a modified WT1 peptide compatible with HLA-A*24:02. The patients received 20 and 25 vaccines, respectively, and experienced no adverse effects aside from a grade 2 skin reaction at the injection site and a fever with tolerable elevation. WT1tetramer analysis after vaccination detected WT1-specific immune responses. This treatment strategy may be safe, tolerable, and even feasible for all patients who are refractory to treatment and for pediatric patients who have relapsed with neoplasms.
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