Combination tumor‐immunotherapy with recombinant tumor necrosis factor and recombinant interleukin 2 in mice
Combination tumor‐immunotherapy with recombinant tumor necrosis factor and recombinant interleukin 2 in mice
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重组肿瘤坏死因子和重组白细胞介素2联合肿瘤免疫治疗小鼠
DOI:
10.1002/ijc.2910400222
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发表时间:
1987
影响因子:
6.4
通讯作者:
Y. Hashimoto
中科院分区:
文献类型:
--
作者:
T. Nishimura;So Ohta;N. Sato;Y. Togashi;M. Goto;Y. Hashimoto
Recombinant human tumor necrosis factor (r‐TNF) inhibits growth of various mouse tumor cell lines both in vitro and in vivo. Treatment of established tumor nodules with intratumoral (i.t.) injection of r‐TNF caused hemorrhagic necrosis of tumor and temporary disappearance of tumor mass. However, a small number of tumor cells remained and later formed fresh nodules. In striking contrast, combination therapy with r‐TNF and recombinant human interleukin‐2 (r‐IL‐2) resulted in a marked inhibition of regrowth of tumor cells. More than 60% of MBL‐2‐bearing mice were completely cured of tumor by treatment with r‐TNF and r‐IL‐2. Cured mice could also reject rechallenged MBL‐2 lymphoma cells, indicating the generation of anti‐tumor effector cells in vivo. However, lymphocytes obtained from mice cured of MBL‐2 showed no significant in vitro cytotoxic activity against MBL‐2 lymphoma cells. In contrast, in vitro sensitization of spleen cells from cured mice with mitomycin‐C‐treated MBL‐2 lymphoma cells resulted in the generation of cytotoxic cells against MBL‐2 lymphoma cells. Moreover, spleen cells from mice cured of MBL‐2 by treatment with r‐TNF and r‐IL‐2 revealed a strong anti‐tumor activity upon in vivo neutralization tests. These results strongly suggest that tumor‐bearing mice can acquire systemic immunological memory after combination therapy with r‐TNF and r‐IL‐2.
影响因子:
56.9
作者:
BEUTLER, B;MILSARK, IW;CERAMI, AC
通讯作者:
CERAMI, AC