PMID- 17208541
OWN - NLM
STAT- MEDLINE
DCOM- 20070205
LR  - 20070108
IS  - 1531-5037 (Electronic)
IS  - 0022-3468 (Linking)
VI  - 42
IP  - 1
DP  - 2007 Jan
TI  - Induction of cytolytic T lymphocytes against pediatric solid tumors in vitro 
      using autologous dendritic cells pulsed with necrotic primary tumor.
PG  - 54-61; discussion 61
AB  - PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
FAU - Shilyansky, Joel
AU  - Shilyansky J
AD  - Division of Pediatric Surgery, Department of Surgery, Medical College of 
      Wisconsin, Milwaukee, WI 53226, USA.
FAU - Jacobs, Paulette
AU  - Jacobs P
FAU - Doffek, Kara
AU  - Doffek K
FAU - Sugg, Sonia L
AU  - Sugg SL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Pediatr Surg
JT  - Journal of pediatric surgery
JID - 0052631
RN  - 0 (Cancer Vaccines)
SB  - IM
MH  - Adolescent
MH  - Cancer Vaccines/*immunology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Child
MH  - Child, Preschool
MH  - Dendritic Cells/*immunology
MH  - Humans
MH  - Infant
MH  - Lymphocyte Activation
MH  - Necrosis
MH  - Neoplasms/immunology/*therapy
MH  - T-Lymphocytes, Cytotoxic/*immunology
EDAT- 2007/01/09 09:00
MHDA- 2007/02/06 09:00
CRDT- 2007/01/09 09:00
PHST- 2007/01/09 09:00 [pubmed]
PHST- 2007/02/06 09:00 [medline]
PHST- 2007/01/09 09:00 [entrez]
AID - S0022-3468(06)00653-1 [pii]
AID - 10.1016/j.jpedsurg.2006.09.008 [doi]
PST - ppublish
SO  - J Pediatr Surg. 2007 Jan;42(1):54-61; discussion 61. doi: 
      10.1016/j.jpedsurg.2006.09.008.