Dendritic Cell-Based Cancer Immunotherapy Targeting Wilms’ Tumor 1 for Pediatric Cancer

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 Shimodaira et al. 114 and interleukin-4, which are the molecules principally attributed to the presence of tumorassociated 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.

Immune expression in children with Wilms tumor: a pilot study

“…Interestingly, however, immunotherapy has rarely been applied to WT itself. One recent case report demonstrated a partial response in an individual patient who ultimately succumbed to her stage IV WT; however, formal phase I reports are to our knowledge lacking on this modality [38]. Clearly, much work remains to improve the prognosis of patients with recurrent and high-risk WT.…”

Role of Immune System in Kidney Cancer

“…According to the cell type where the tumor starts, kidney cancers are classified as renal cell carcinoma (RCC) subdivided in papillary RCC, chromophobe RCC, rare types of RCC, and unclassified RCC. Also, there are transitional cell carcinoma, Wilms' tumor, which almost always occur in children and renal sarcoma [1][2][3][4].…”

“…Regardless of the category, kidney tumors have been associated with immune dysfunction [1][2][3]5]. RCCs are rich in immune infiltrates consisting of T cells, natural killer (NK), DCs, macrophages among others [6,7].…”

In Vivo Administration of Recombinant Human Granulocyte Colony-Stimulating Factor Increases the Immune Effectiveness of Dendritic Cell-Based Cancer Vaccination

“…The US Food and Drug Administration approved sipuleucel-T (Provenge ® , Dendreon Corporation, Seattle, WA, USA) as autologous DC-based immunotherapy for patients with metastatic hormone-refractory prostate cancer, providing a new personalized cancer immunotherapy treatment option [11]. DC vaccines targeting Wilms’ tumor 1 (WT1) have been previously shown to be safe and feasible with few adverse reactions in patients with advanced cancer, including colorectal cancer [12], pancreatic cancer [13,14], lung cancer [15], high-grade glioma [16], and pediatric cancer [17,18]. The efficacy of DC-based immunotherapy is more evidently demonstrated by the delayed separation of the survival curve with a benefit in terms of prolonged overall survival rather than conventional evaluation approaches such as the use of the response rates [13,15,19].…”