Allogeneic gastric cancer cell-dendritic cell hybrids induce tumor antigen (carcinoembryonic antigen) specific CD8(+) T cells.
The development of protocols for the ex vivo generation of dendritic cells (DCs) has led to intensive research of their potential use in immunotherapy. Accumulating results show the efficacy of this treatment on melanomas which are highly immunogenic. However, its efficacy remains unclear in other tumors. In this study, allogeneic gastric cancer cell-DC hybrids were used to determine the efficacy of this type of immunotherapy in gastric cancer. Fusion cells of DC and allogeneic gastric cancer cells were generated by polyethylene glycol (PEG) and electrofusion. These hybrids were used to induce tumor associated antigen (TAA) specific cytotoxic T lymphocytes (CTLs). The DCs were successfully fused with the allogeneic gastric cancer cells resulting in hybrid cells. These hybrid cells were functional as antigen-presenting cell because they induced allogeneic CD4(+) T cells proliferation. CD8(+) T cells stimulated by the MKN-45-DC hybrid cells were able to kill MKN-45 when used for immunization. The CTLs killed another gastric cancer cell line, MKN-1, as well as a melanoma cell line, 888mel, suggesting the recognition of a shared tumor antigen. MKN-45 specific CTLs can recognize carcinoembryonic antigen (CEA), indicating that the killing is due to tumor antigens as well as alloantigens. This approach suggests the possible use of allogeneic gastric cancer cell-DC hybrids in DC based immunotherapy for gastric cancer treatment.
Matsumoto
Sachiko
S
Division of Surgical Oncology, Tottori University School of Medicine, 36-1 Nishi-cho, Yonago 683-8504, Japan.
Saito
Hiroaki
H
Tsujitani
Shunichi
S
Ikeguchi
Masahide
M
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002459:Cell Fusion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D004558:Electric Stimulation; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology; D013274:Stomach Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D002272:Carcinoembryonic Antigen; D007519:Isoantigens