PMID- 11912169
OWN - NLM
STAT- MEDLINE
DCOM- 20020429
LR  - 20201219
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 62
IP  - 6
DP  - 2002 Mar 15
TI  - Strategies for antigen loading of dendritic cells to enhance the antitumor immune 
      response.
PG  - 1884-9
AB  - Dendritic cells (DCs) primed with tumor antigens can effectively mediate the 
      regression of a variety of established solid malignancies in both murine and 
      human models. Despite such clinical efficacy, the optimal means of DC priming is 
      unknown. The goal of this study was to compare three methods of tumor 
      preparation: irradiation, boiling, or freeze thaw lysis for DC priming. Mouse 
      bone marrow-derived DCs were loaded with defined ratios of E.G7 tumor cells 
      expressing a model tumor antigen, OVA. Sensitized DCs were used for stimulation 
      of OVA-specific CTLs derived from OT-1 T-cell receptor transgenic mice. IFN-gamma 
      release, determined by ELISA at 24 and 48 h, was used to assess the expression of 
      antigens by DCs. DCs loaded with irradiated tumors were effective stimulators for 
      OT-1 CTLs, whereas DCs stimulated with freeze-thawed or boiled tumors did not 
      stimulate IFN-gamma production. Freeze-thaw lysis appeared to inhibit CTL 
      activity in vitro and in two of three cases, this effect was not overcome by the 
      addition of OVA. The ability to load irradiated tumor cells was reproduced in two 
      analogous human melanoma models using melanoma cell lines expressing gp100 and 
      CTL clones specific for a gp100 melanoma antigen. Consistent with the in vitro 
      data, only DC/irradiated tumor vaccines were effective in preventing or delaying 
      outgrowth of E.G7 and a poorly immunogenic murine squamous cell carcinoma 
      (SCCVII), on local tumor challenge. These data demonstrate that the method of 
      tumor cell preparation clearly influences the ability of DCs to present antigen 
      to T cells. Correlation of in vitro data with the generation of protective 
      immunity in vivo suggests the utility of irradiated tumor-primed DCs as a means 
      to generate protective immunity in patients with solid malignancies.
FAU - Strome, Scott E
AU  - Strome SE
AD  - Department of Otolaryngology, Mayo Clinic, Rochester, Minnesota 55905, USA. 
      strome.scott@mayo.edu
FAU - Voss, Stephen
AU  - Voss S
FAU - Wilcox, Ryan
AU  - Wilcox R
FAU - Wakefield, Tamekia L
AU  - Wakefield TL
FAU - Tamada, Koji
AU  - Tamada K
FAU - Flies, Dallas
AU  - Flies D
FAU - Chapoval, Andrei
AU  - Chapoval A
FAU - Lu, Jun
AU  - Lu J
FAU - Kasperbauer, Jan L
AU  - Kasperbauer JL
FAU - Padley, Douglas
AU  - Padley D
FAU - Vile, Richard
AU  - Vile R
FAU - Gastineau, Dennis
AU  - Gastineau D
FAU - Wettstein, Peter
AU  - Wettstein P
FAU - Chen, Lieping
AU  - Chen L
LA  - eng
GR  - CA85721/CA/NCI NIH HHS/United States
GR  - K23DE00459/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Animals
MH  - Antigen Presentation/immunology
MH  - Antigens, Neoplasm/*immunology
MH  - Apoptosis/immunology
MH  - Cancer Vaccines/*immunology
MH  - Carcinoma, Squamous Cell/immunology/pathology
MH  - Dendritic Cells/*immunology
MH  - Freezing
MH  - Heating
MH  - Humans
MH  - Immunotherapy, Adoptive/*methods
MH  - Melanoma/immunology/pathology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Necrosis
MH  - Neoplasms, Experimental/*immunology/therapy
MH  - Ovalbumin/immunology
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Thymoma/immunology/pathology
MH  - Tumor Cells, Cultured/radiation effects
EDAT- 2002/03/26 10:00
MHDA- 2002/05/01 10:01
CRDT- 2002/03/26 10:00
PHST- 2002/03/26 10:00 [pubmed]
PHST- 2002/05/01 10:01 [medline]
PHST- 2002/03/26 10:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2002 Mar 15;62(6):1884-9.