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However, a small number of tumor cells remained and later formed fresh nodules. In striking contrast, combination therapy with r\u2010TNF and recombinant human interleukin\u20102 (r\u2010IL\u20102) resulted in a marked inhibition of regrowth of tumor cells. More than 60% of MBL\u20102\u2010bearing mice were completely cured of tumor by treatment with r\u2010TNF and r\u2010IL\u20102. Cured mice could also reject rechallenged MBL\u20102 lymphoma cells, indicating the generation of anti\u2010tumor effector cells <jats:italic>in vivo.<\/jats:italic> However, lymphocytes obtained from mice cured of MBL\u20102 showed no significant <jats:italic>in vitro<\/jats:italic> cytotoxic activity against MBL\u20102 lymphoma cells. In contrast, <jats:italic>in vitro<\/jats:italic> sensitization of spleen cells from cured mice with mitomycin\u2010C\u2010treated MBL\u20102 lymphoma cells resulted in the generation of cytotoxic cells against MBL\u20102 lymphoma cells. Moreover, spleen cells from mice cured of MBL\u20102 by treatment with r\u2010TNF and r\u2010IL\u20102 revealed a strong anti\u2010tumor activity upon <jats:italic>in vivo<\/jats:italic> neutralization tests. These results strongly suggest that tumor\u2010bearing mice can acquire systemic immunological memory after combination therapy with r\u2010TNF and r\u2010IL\u20102.<\/jats:p>","DOI":"10.1002\/ijc.2910400222","type":"journal-article","created":{"date-parts":[[2007,2,19]],"date-time":"2007-02-19T21:10:17Z","timestamp":1171919417000},"page":"255-261","source":"Crossref","is-referenced-by-count":36,"title":["Combination tumor\u2010immunotherapy with recombinant tumor necrosis factor and recombinant interleukin 2 in mice"],"prefix":"10.1002","volume":"40","author":[{"given":"Takashi","family":"Nishimura","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So","family":"Ohta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoko","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Togashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makiko","family":"Goto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiyuki","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,17]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/316552a0"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3895437"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.9.3666"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60308-9"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.4049\/jimmunol.134.2.1026","article-title":"Stimulated rat T cell\u2010Derived inhibitory factor for cellular DNA synthesis (sTIF). 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