Artificial cytokine storm combined with hyperthermia induces significant anti-tumor effect in mice inoculated with lewis lung carcinoma and B16 melanoma cells.
In cancer immunotherapies combined with hyperthermia, one or two cytokines have been tested to augment the anti-tumor effect. However, the therapies have not shown sufficient improvement. The aim of this study is to find a new potent tumor immunotherapy in order to augment antitumor effect of hyperthermia by the cytokine cocktails in vivo. We used a combination therapy of local hyperthermia (LH) and various cytokine cocktails composed of IFNs (IFN-alpha, -beta, and -gamma), Thl cytokines (IL-2, -12, -15, and -18), a Th2 cytokine (IL-4), inflammatory cytokines (IL-lalpha and TNF-alpha), and dendritic cell-inducible cytokines (IL-3 and GM-CSF). These cytokines in a proper combination augmented the anti-tumor effect of LH and prolonged survival time in Lewis lung carcinoma or B16 melanoma significantly. Moreover, the 12-cytokine cocktail suppressed B 16 metastasis to the lung and lymph nodes, and complete regression of the tumors without regrowth occurred in 3 of 5 mice. In the cured three B16 mice, there was hyperplasia of lymphatic organs with many CD3-positive T lymphocytes. The most effective cytokine combination should be able to augment the anti-tumor effect of other therapies besides hyperthermia that induce the necrosis of tumor cells.
Kushida
Shigeki
S
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8575, Japan. skushida@beige.ocn.ne.jp
Ohmae
Hiroshi
H
Kamma
Hiroshi
H
Totsuka
Rumiko
R
Matsumura
Masayuki
M
Takeuchi
Akira
A
Saiki
Ikuo
I
Yanagawa
Toru
T
Onizawa
Kojiro
K
Ishii
Tetsuro
T
Ohn
Tadao
T
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000628:therapy*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006979:Hyperthermia, Induced; D016233:Immunotherapy, Active / Q000379:methods*; D008297:Male; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D016019:Survival Analysis; D016896:Treatment Outcome
D016207:Cytokines