Combination tumor-immunotherapy with recombinant tumor necrosis factor and recombinant interleukin 2 in mice

✍ Scribed by Takashi Nishimura; So Ohta; Naoko Sato; Yuji Togashi; Makiko Goto; Yoshiyuki Hashimoto

• Publisher: John Wiley and Sons
• Year: 1987
• Tongue: French
• Weight: 656 KB
• Volume: 40
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910400222

✦ Synopsis

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 MBLJ 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.