Anti-tumor immunostimulatory effect of heat-killed tumor cells.
As a part of our ongoing search for a safe and efficient anti-tumor vaccine, we attempted to determine whether the molecular nature of certain tumor antigens would influence immune responses against tumor cells. As compared with freeze-thawed or formaldehyde-fixed tumor antigens, heat-denatured tumor antigens elicited profound anti-tumor immune responses and greatly inhibited the growth of live tumor cells. The heat-denatured tumor antigens induced a substantial increase in the anti-tumor CTL response in the absence of any adjuvant material. This response appears to be initiated by strong activation of the antigen-presenting cells, which may recognize heat-denatured protein antigens. Upon recognition of the heat-denatured tumor antigens, macrophages and dendritic cells were found to acutely upregulate the expression of co-stimulatory molecules such as B7.2, as well as the secretion of inflammatory cytokines such as IL-12 and TNF-alpha. The results of this study indicate that heat-denatured tumor extracts might elicit protective anti-tumor adaptive immune responses and also raise the possibility that a safe and efficient adjuvant-free tumor vaccine might be developed in conjunction with a dendritic cell-based tumor vaccine.
Yoon
Taek Joon
TJ
MD Bioalpha Inc., Suwon 443-813, Korea.
Kim
Ji Yeon
JY
Kim
Hyojeong
H
Hong
Changwan
C
Lee
Hyunji
H
Lee
Chang Kwon
CK
Lee
Kwang Ho
KH
Hong
Seokmann
S
Park
Se Ho
SH
D000276:Adjuvants, Immunologic; D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006358:Hot Temperature; D007111:Immunity, Cellular / Q000276:immunology; D007114:Immunization; D007156:Immunologic Memory / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology*; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines