Prophylactic Antitumor Effect of Mixed Heat Shock Proteins/Peptides in Mouse Sarcoma.
BACKGROUND
To develop a vaccine-based immunotherapy for sarcoma, we evaluated a mixture of heat shock proteins (mHSPs) as a vaccine for sarcoma treatment in a mouse model. Heat shock protein/peptides (HSP/Ps) are autoimmune factors that can induce both adaptive and innate immune responses; HSP/Ps isolated from tumors can induce antitumor immune activity when used as vaccines.


METHODS
In this study, we evaluated the effects of mHSP/Ps on prophylactic antitumor immunity. We extracted mHSP/Ps, including HSP60, HSP70, GP96, and HSP110, from the mouse sarcoma cell lines S180 and MCA207 using chromatography. The immunity induced by mHSP/Ps was assessed using flow cytometry, ELISPOT, lactate dehydrogenase release, and enzyme-linked immunosorbent assay.


RESULTS
Of S180 sarcoma-bearing mice immunized with mHSP/Ps isolated from S180 cells, 41.2% showed tumor regression and long-term survival, with a tumor growth inhibition rate of 82.3% at 30 days. Of MCA207 sarcoma-bearing mice immunized with mHSP/Ps isolated from MCA207 cells, 50% showed tumor regression and long-term survival with a tumor growth inhibition rate of 79.3%. All control mice died within 40 days. The proportions of natural killer cells, CD8+, and interferon-γ-secreting cells and tumor-specific cytotoxic T-lymphocyte activity were increased in the immunized group.


CONCLUSIONS
Vaccination with a polyvalent mHSP/P cancer vaccine can induce an immunological response and a marked antitumor response to autologous tumors. This mHSP/P vaccine exerted greater antitumor effects than did HSP70, HSP60, or tumor lysates alone.
Yu
Y
Wang
Shu-Yun
SY
Liu
Mei
M
Yuan
Yu
Y
Tang
Quan-Yi
QY
Guo
Xue-Mei
XM
Cui
Xiang
X
Sui
Institute of Orthopedics, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
Jiang
J
Peng
D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005260:Female; D006360:Heat-Shock Proteins / Q000008:administration & dosage*; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000008:administration & dosage; D012513:Sarcoma, Experimental / Q000517:prevention & control*; D014611:Vaccination
D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; D010455:Peptides