Exp Mol Med.  2008 Feb;40(1):130-144. 10.3858/emm.2008.40.1.130.

Anti-tumor immunostimulatory effect of heat-killed tumor cells

• Yoon TJ
• Kim JY
• Kim H
• Hong C
• Lee H
• Lee CK
• Lee KH
• Hong S
• Park SH

• KMID: 1103596
• DOI: http://doi.org/10.3858/emm.2008.40.1.130

Abstract

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.

Keyword

cancer vaccines; dendritic cells; immunotherapy, active; interleukin 12; mice

MeSH Terms

Adjuvants, Immunologic
Animals
Antibodies, Neoplasm/immunology
Antibody Specificity/immunology
Antigens, Neoplasm/immunology
Cancer Vaccines/*immunology
Cell Line, Tumor
Cell Proliferation
Cytokines/biosynthesis
Cytotoxicity, Immunologic/immunology
Dendritic Cells/immunology
*Hot Temperature
Immunity, Cellular/immunology
Immunization
Immunologic Memory/immunology
Macrophages, Peritoneal/immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Neoplasms/*immunology/*pathology
Survival Analysis
T-Lymphocytes, Cytotoxic/immunology