Journal article
Induction of cytolytic T lymphocytes against pediatric solid tumors in vitro using autologous dendritic cells pulsed with necrotic primary tumor
Journal of pediatric surgery, Vol.42(1), pp.54-61
01/2007
DOI: 10.1016/j.jpedsurg.2006.09.008
PMID: 17208541
Abstract
Effective and generally applicable methods for generating cancer vaccines in children have not been defined. Dendritic cells (DCs) are the most potent professional antigen-presenting cells capable of activating primary cytolytic T cells. We tested the ability of DCs generated from pediatric patients' peripheral blood monocytes and pulsed with a necrotic tumor to activate autologous tumor-specific cytolytic T cells.
Tumor and peripheral blood cells were obtained from pediatric patients undergoing biopsy or resection for advanced solid tumors according to an institutional research board-approved protocol and after acquiring informed consent from them. To generate DCs, we treated peripheral blood monocytes with granulocyte-macrophage colony stimulating factor and interleukin (IL)-4. Maturation was induced with a cytokine cocktail (CC) containing tumor necrosis factor-alpha, IL-6, IL-1beta, and prostaglandin E2. The DC phenotype was assayed using flow cytometry. Tumor necrosis was induced by exposure to UV-B irradiation (1000 mJ). Dendritic cells pulsed with a UV-B-treated primary tumor and matured with CC were used to stimulate autologous peripheral blood lymphocytes weekly. Tumor-specific cytolytic activity was assayed using 4-hour 51Cr release.
Peripheral blood monocytes isolated from pediatric patients differentiated into immature DCs (CD14-, MHCII+ [major histocompatibility complex], CD80(low), CD86(low)) in the presence of granulocyte-macrophage colony stimulating factor and IL-4. Cytokine cocktail induced maturation of DCs, as characterized by increased expressions of MHCII, CD83, CD80, and CD86. Patients' peripheral blood lymphocytes stimulated in vitro with DCs loaded with a necrotic primary tumor and matured with CC specifically lysed autologous neuroblastoma in 7 of 9 patients.
Dendritic cells generated from the peripheral blood of children with advanced solid tumors and pulsed with a necrotic primary tumor undergo maturation and effectively stimulate autologous tumor-specific cytolytic T cells in vitro. We describe a simple method for generating a vaccine capable of activating cytotoxic T cells against pediatric solid tumors that does not require the genetic identification of tumor-associated antigens.
Details
- Title: Subtitle
- Induction of cytolytic T lymphocytes against pediatric solid tumors in vitro using autologous dendritic cells pulsed with necrotic primary tumor
- Creators
- Joel Shilyansky - Division of Pediatric Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USAPaulette JacobsKara DoffekSonia L Sugg
- Resource Type
- Journal article
- Publication Details
- Journal of pediatric surgery, Vol.42(1), pp.54-61
- Publisher
- United States
- DOI
- 10.1016/j.jpedsurg.2006.09.008
- PMID
- 17208541
- ISSN
- 0022-3468
- eISSN
- 1531-5037
- Language
- English
- Date published
- 01/2007
- Academic Unit
- Stead Family Department of Pediatrics; Surgery
- Record Identifier
- 9984051894202771
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