Giampietri A, Bonmassar A, Puccetti P, Circolo A, Goldin A, Bonmassar E
Cancer Res. 1981 Feb;41(2):681-7.
In vivo treatment of leukemic mice with the antitumor agent 5-(3,3'-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) results in early increase of tumor-associated immunogenicity which is expected to evoke host-versus-graft responses. However, transplantation immunity is severely impaired in DTIC-treated mice due to the immunodepressant activity of the drug. It follows that the DTIC-mediated increase of tumor immunogenicity effect cannot be of therapeutic value in ordinary conditions. In the present report, we describe the results of studies aimed at restoring immunocompetence of DTIC-treated mice by means of adoptive transfer of syngeneic lymphoid cells. Infusion of spleen cells into DTIC-treated mice failed to restore graft responsiveness even in allogeneic tumor-host combinations. However, when DTIC treatment was followed by administration of cytotoxic alkylating agents such as cyclophosphamide (CY) or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), graft responsiveness was partially restored upon adoptive transfer of syngeneic splenocytes. (BALB/c X DBA/2) F1 (hereafter called CD2F1) mice bearing leukemia L1210 Ha were treated as follows: (a) DTIC for increasing the immunogenicity of the leukemic cells; (b) CY or BCNU; and (c) adoptive transfer of CD2F1 lymphocytes. The results showed that: (a) DTIC alone or DTIC plus spleen cells produced little or no increase in survival times with respect to untreated controls; (b) DTIC plus CY or BCNU increased survival times to a larger extent; and (c) the adoptive transfer of lymphocytes produced marked protection of leukemic mice when the hosts had been pretreated with DTIC plus CY or BCNU but not with CY or BCNU without DTIC. These data may provide a model for exploiting DTIC-induced increase of tumor immunogenicity for immunochemotherapeutic regimens.
用抗肿瘤剂5-(3,3'-二甲基-1-三氮烯)-咪唑-4-甲酰胺（DTIC）对白血病小鼠进行体内治疗，会导致肿瘤相关免疫原性早期增加，这有望引发宿主对移植物的反应。然而，由于该药物的免疫抑制活性，DTIC治疗的小鼠的移植免疫严重受损。因此，在通常情况下，DTIC介导的肿瘤免疫原性增加效应没有治疗价值。在本报告中，我们描述了旨在通过同基因淋巴细胞的过继转移来恢复DTIC治疗小鼠免疫能力的研究结果。将脾细胞注入DTIC治疗的小鼠中，即使在同种异体肿瘤宿主组合中也未能恢复移植物反应性。然而，当DTIC治疗后给予细胞毒性烷化剂如环磷酰胺（CY）或1,3-双(2-氯乙基)-1-亚硝基脲（BCNU）时，同基因脾细胞的过继转移可部分恢复移植物反应性。携带白血病L1210 Ha的（BALB/c×DBA/2）F1（以下称为CD2F1）小鼠按以下方式处理：（a）用DTIC增加白血病细胞的免疫原性；（b）用CY或BCNU；（c）过继转移CD2F1淋巴细胞。结果显示：（a）单独使用DTIC或DTIC加脾细胞相对于未处理的对照组，存活时间几乎没有增加或没有增加；（b）DTIC加CY或BCNU可更大程度地延长存活时间；（c）当宿主先用DTIC加CY或BCNU预处理而不是用CY或BCNU且未用DTIC预处理时，淋巴细胞的过继转移对白血病小鼠产生了显著的保护作用。这些数据可为利用DTIC诱导的肿瘤免疫原性增加进行免疫化疗方案提供一个模型。
