Ohe Y, Podack E R, Olsen K J, Miyahara Y, Ohira T, Miura K, Nishio K, Saijo N
Department of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan.
Int J Cancer. 1993 Feb 1;53(3):432-7. doi: 10.1002/ijc.2910530314.
In order to develop a more effective method of immunotherapy we have transfected mouse interleukin-2 (IL2) or mouse interleukin-4 (IL4) cDNA into a spontaneous non-immunogenic murine lung cancer. Lewis lung carcinoma (LLC). IL2 cDNA transfection more strongly decreases tumorigenicity of LLC than IL4 cDNA transfection. Recombinant-human-IL2 treatment of mice that were transplanted with untransfected LLC could not prolong their survival. In contrast, vaccination with IL2-cDNA-transfected LLC (LLC-IL2) and LLC-IL2 mixed with IL4-cDNA-transfected LLC (LLC-IL4) could significantly suppress tumor growth of LLC in a tumor-specific manner. The vaccination with LLC-IL2 mixed with the same number of LLC-IL4 cells was more suppressive to the growth of LLC than that with LLC-IL2 cells alone, while LLC-IL4 vaccination alone was ineffective. Nude, severe-combined-immune-deficient (SCID) and beige mice were unable to reject LLC-IL2 cells. However, immunodeficient mice responded to LLC-IL2, but not to LLC, since their survival times after transplantation with LLC-IL2 cells were significantly longer than the survival time of normal or immunodeficient mice transplanted with untransfected LLC cells. We conclude that vaccination with IL2-producing tumors and, with more pronounced effect, in combination with IL4-producing tumors, is able to induce an immune response to this normally non-immunogenic tumor. Tumor rejection appears to be achieved by the combined activity of CTL and NK cells. This strategy has potential for new immunotherapeutic interventions in cancer patients.
为了开发一种更有效的免疫治疗方法，我们已将小鼠白细胞介素-2（IL2）或小鼠白细胞介素-4（IL4）cDNA转染到一种自发的非免疫原性小鼠肺癌——Lewis肺癌（LLC）中。与IL4 cDNA转染相比，IL2 cDNA转染更能显著降低LLC的致瘤性。用重组人IL2治疗移植了未转染LLC的小鼠并不能延长其生存期。相比之下，用IL2 cDNA转染的LLC（LLC-IL2）以及与IL4 cDNA转染的LLC（LLC-IL4）混合的LLC-IL2进行疫苗接种，能够以肿瘤特异性方式显著抑制LLC的肿瘤生长。用相同数量的LLC-IL4细胞与LLC-IL2混合进行疫苗接种比单独使用LLC-IL2细胞对LLC生长的抑制作用更强，而单独用LLC-IL4进行疫苗接种则无效。裸鼠、严重联合免疫缺陷（SCID）小鼠和米色小鼠无法排斥LLC-IL2细胞。然而，免疫缺陷小鼠对LLC-IL2有反应，但对LLC无反应，因为它们移植LLC-IL2细胞后的存活时间明显长于移植未转染LLC细胞的正常或免疫缺陷小鼠的存活时间。我们得出结论，用产生IL2的肿瘤进行疫苗接种，以及更显著地与产生IL4的肿瘤联合接种，能够诱导针对这种通常非免疫原性肿瘤的免疫反应。肿瘤排斥似乎是通过CTL和NK细胞的联合作用实现的。这种策略在癌症患者的新型免疫治疗干预方面具有潜力。
