Shimizu Y, Hasumi K, Masubuchi K, Okudaira Y
Department of Gynecology, Cancer Institute Hospital, Tokyo, Japan.
Cancer Immunol Immunother. 1988;27(3):223-7. doi: 10.1007/BF00205443.
Utilizing vaccinia virus (VV), a tumor-specific immunotherapy model was established in which a growing tumor regressed. C3H/HeN mice were primed with VV after low dose irradiation to generate amplified VV-reactive T cell activities. Then 4 weeks later, the mice were inoculated i.d. with syngeneic MH134 hepatoma cells, and 6 days after the tumor cell inoculation, live VV was injected into the tumor mass 3 times at 2-day intervals. Of 10 mice which had received VV priming and subsequent VV injection into the tumor mass, 8 exhibited complete tumor regression. On the contrary, mice which had received only intratumoral VV injection without VV priming failed to exhibit appreciable tumor regression. Mice whose tumor had completely regressed following the VV immunotherapy were shown to have acquired systemic antitumor immunity, which was confirmed by a challenge with syngeneic tumor cells after immunotherapy. In vitro analysis of these immune mice revealed that potent tumor-specific antibody responses were preferentially induced, but with no detectable antitumor cytotoxic T lymphocyte (CTL) responses. Such a potent tumor-specific immunity was not observed in mice which had received intratumoral VV injection in the absence of VV priming. Thus, the results clearly indicate that tumor regression was accompanied by the concurrent generation of a potent tumor-specific immunity, suggesting that cellular cooperation between VV-reactive T cells and tumor-specific effector cells might be functioning in this VV immunotherapy protocol. Therefore, the present model provides an effective maneuver for tumor-specific immunotherapy. This system is, in principle, applicable to the human situation.
利用痘苗病毒（VV），建立了一种肿瘤特异性免疫治疗模型，在该模型中生长的肿瘤发生了消退。对C3H/HeN小鼠进行低剂量照射后用VV进行预处理，以产生增强的VV反应性T细胞活性。然后在4周后，给小鼠皮下接种同基因的MH134肝癌细胞，在接种肿瘤细胞6天后，将活的VV以2天的间隔分3次注射到肿瘤块中。在接受VV预处理并随后将VV注射到肿瘤块中的10只小鼠中，有8只肿瘤完全消退。相反，仅接受肿瘤内VV注射而未进行VV预处理的小鼠未能表现出明显的肿瘤消退。在VV免疫治疗后肿瘤完全消退的小鼠被证明获得了全身抗肿瘤免疫力，这在免疫治疗后用同基因肿瘤细胞进行攻击时得到了证实。对这些免疫小鼠的体外分析显示，优先诱导了强效的肿瘤特异性抗体反应，但未检测到抗肿瘤细胞毒性T淋巴细胞（CTL）反应。在未进行VV预处理的情况下接受肿瘤内VV注射的小鼠中未观察到这种强效的肿瘤特异性免疫力。因此，结果清楚地表明肿瘤消退伴随着同时产生强效的肿瘤特异性免疫力，这表明VV反应性T细胞与肿瘤特异性效应细胞之间的细胞合作可能在这种VV免疫治疗方案中发挥作用。因此，本模型为肿瘤特异性免疫治疗提供了一种有效的策略。该系统原则上适用于人类情况。
