OBJECTIVE: To establish the basis for use of allogeneic dendritic-tumor fusion cells.
STUDY DESIGN: Fusion cells were created by electrofusion. We used 2 allogeneic murine tumor lines (D5 and 4T1) that were virally transduced to express the antigen (β-galactosidase) as a surrogate tumor marker.
RESULTS: Cross-immunization was achieved with irradiated allogenic tumor cells. Successful electrofusion of dendritic cells and tumor cells was confirmed by using fluorescence-activated cell sorting and cytospin. Significant responses were shown in immunized mice against tumor challenge and established 3-day pulmonary metastasis with fusion cells.
CONCLUSIONS: Allogeneic tumor sharing a common tumor antigen can immunize against syngeneic tumor challenge. Fusion cells showed successful immunization against tumor challenge and showed regression of 3-day established pulmonary metastasis.
SIGNIFICANCE: These preclinical studies provide evidence that an allogenic tumor-dendritic cell fusion vaccine is a valid approach for head and neck cancer immunotherapy. (Otolaryngol Head Neck Surg 2005;132:755-64.)
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References
1.
JemalAMurrayTSamelsA. Cancer Statistics, 2003. CA Cancer J Clin2003; 53:5–26.
2.
LandisSHMurrayTBoldenS. Cancer Statistics, 1999. CA Cancer J Clin1999; 49:8–31.
3.
ToWCSeeleyBMBarthelSW. Therapeutic efficacy of Th1 and Th2 L-selectin- CD4+ tumor reactive T cells. Laryngoscope2000; 110:1648–54.
4.
SteinmanRM.The dendritic cell system and its role in immunogenicity. Annu Rev Immunol1991; 9:271–96.
5.
Nouri-ShiraziMBanchereauJFayJ. Dendritic cell based tumor vaccines. Immunol Lett2000; 74:5–10.
6.
BanchereauJBriereFCauxC. Immunology of dendritic cells. Annu Rev Immunol2000; 18:767–811.
7.
SteinmanRMDhodapkarM.Active immunization against cancer with dendritic cells: the near future. Int J Cancer2001; 94:459–73.
HayashiTTanakaHTanakaJ. Immunogenicity and therapeutic efficacy of dendritic-tumor hybrid cells generated by electrofusion. Clin Immunol2002; 104:14–20.
10.
KjaergaardJShimizuKShuS.Electrofusion of syngeneic dendritic cells and tumor generates potent therapeutic vaccine. Cell Immunol2003; 225:65–74.
11.
KimCJDessureaultSGabrilovichD. Immunotherapy for melanoma. Cancer Control2001; 9:22–30.
12.
MortonDLFoshagLJHoonDSB. Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine. Ann Surg1992; 216:463–82.
13.
KrauseCJCareyTEOttRW. Human squamous cell carcinoma. Arch Otolaryngol1981; 107:703–10.
14.
TanakaHShimizuKHayashiT. Therapeutic immune response induced by electrofusion of dendritic and tumor cells. Cell Immunol2002; 220:1–12.
15.
TatsumiTTakeharaTKantoT. Administration of interleukin-12 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines in mouse hepatocellular carcinoma. Cancer Res2001; 61:7563–7.
16.
Scott-TaylorTHPettengellRClarkeI. Human tumour and dendritic cell hybrids generated by electrofusion: potential for cancer vaccines. Biochim Biophys Acta2000; 1500:265–79.
17.
ParkhurstMRDePanCRileyJP. Hybrids of dendritic cells and tumor cells generated by electrofusion simultaneously present immunodominant epitopes form multiple human tumor-associated antigens in the context of MHC class I and class II molecules. J Immunol2003; 170; 5317–25.
