Therapeutic efficacy of tumor-derived heat shock protein 70 immunotherapy combining interleukin-2 on tumor-bearing mice.
OBJECTIVE
To investigate the therapeutic efficacy of compound immunotherapy of tumor-derived heat shock protein 70 (HSP70) and interleukin-2 (IL-2) on tumor-bearing mice, and to provide reference for translating this strategy to human cancer.


METHODS
Cell culture, techniques for protein extraction and purification, SDS-PAGE, Western blot and capillary electrophoresis for HSP70 detection and purity analysis, and animal experiments were used. Mice were treated with HSP70 5 or 10 microg and IL-2 50 kU, 100 kU or 2 kU (maintaining dosage) at previously designated intervals.


RESULTS
Both the mono-administration of either HSP70 or IL-2 and the compound immunotherapy of HSP70 and IL-2 obviously inhibited the growth of the implanted tumor and prolonged the life span of the mice to different extents. However, long periods of tumor-free survival (over 90 days) were demonstrated only in HSP70 10 micro g group, HSP70 10 microg-IL-2 50 kU group, and HSP70 10 microg-IL-2 100 kU group (40%, 40%, 60% respectively). On the other hand, none of the mice in the rest groups achieved long-term survival. Statistical significance was apparent in comparison with the groups without long period survival (P < 0.025 - 0.05).


CONCLUSIONS
Our research revealed that tumor-derived HSP70 immunotherapy was much more effective than IL-2 alone. And in compound immunotherapy, HSP70 was the main factor in delaying or eradicating the tumors. The proper combination of HSP70 and IL-2 (10 microg HSP70 and 100 kU IL-2 in this experimental mouse model) clearly enhanced the immunotherapy efficacy which indicated that the specific immunotherapy as a main part of tumor immunotherapy assisted by cytokine immunotherapy would be a promising strategy in cancer treatment.
Fu
Qingguo
Q
The Second General Surgery Department, The First Affiliated Hospital of China Medical University, Shenyang 110001, China. Qingguofu@hotmail.com
Meng
Fandong
F
Shen
Xiaodong
X
Guo
Renxuan
R
D000818:Animals; D004359:Drug Therapy, Combination; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D018840:HSP70 Heat-Shock Proteins; D007376:Interleukin-2