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Combination tumor‐immunotherapy with recombinant tumor necrosis factor and recombinant interleukin 2 in mice
Author(s) -
Nishimura Takashi,
Ohta So,
Sato Naoko,
Togashi Yuji,
Goto Makiko,
Hashimoto Yoshiyuki
Publication year - 1987
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910400222
Subject(s) - recombinant dna , immunotherapy , tumor necrosis factor alpha , tumor necrosis factor α , medicine , interleukin , immunology , interleukin 2 , cytokine , cancer research , biology , immune system , gene , biochemistry
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.