Eradication of a large MOPC-315 tumor in athymic nude mice by chemoimmunotherapy with Lyt2+ splenic T cells from melphalan-treated BALB/c mice bearing a large MOPC-315 tumor.
Eradication of a large MOPC-315 tumor in athymic nude mice by chemoimmunotherapy with Lyt2+ splenic T cells from melphalan-treated BALB/c mice bearing a large MOPC-315 tumor.
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使用来自经美法仑治疗的携带大 MOPC-315 肿瘤的 BALB/c 小鼠的 Lyt2 脾 T 细胞进行化学免疫治疗，消除无胸腺裸鼠中的大 MOPC-315 肿瘤。
DOI：
10.1007/bf01744726
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Mokyr,MB
中科院分区：
文献类型：
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作者：
Weiskirch,LM;Barker,E;Mokyr,MB
我们先前已经表明，BALB/c小鼠的脾细胞在低剂量的抗肿瘤药物治疗后，（2.5 mg/kg）美法仑（L-苯丙氨酸氮芥）疗法在过继转移到带有几乎不可触及的肿瘤的BALB/c小鼠中时有效地防止肿瘤进展，所述肿瘤已经用亚治疗剂量的美法仑治疗[Mokyr等（1989）Cancer Res 49：4597]。在这里，我们表明，这种脾细胞与亚治疗剂量的药物（过继性化学免疫疗法，ACIT）结合可以导致大（15-20 mm）的s.c. MOPC-315肿瘤在很大比例的T细胞缺陷型（无胸腺裸）荷瘤小鼠中。在无胸腺裸鼠ACIT中有效的脾细胞在体外显示出对MOPC-315肿瘤细胞的实质性直接裂解活性，并且当脾细胞与或不与丝裂霉素-C处理的MOPC-315刺激肿瘤细胞一起培养5天时，裂解活性大大增强。在无胸腺裸鼠ACIT中负责脾细胞治疗有效性的细胞以及负责脾细胞直接体外抗MOPC-315裂解活性的细胞为Lyt 2而非L3 T4表型。由于ACIT而完全根除大MOPC-315肿瘤的大多数无胸腺裸鼠能够在ACIT后超过1个月接受给药的100%正常BALB/c小鼠的最小致死肿瘤剂量的30-100倍的攻击。这些无胸腺裸鼠抵抗肿瘤攻击的能力与其脾脏中表达T细胞表面标志物的细胞百分比大大升高有关。因此，可以想象，来自携带大MOPC-315肿瘤的美法仑处理的BALB/c小鼠的脾Lyt 2+T细胞至少部分通过对MOPC-315肿瘤细胞的直接细胞毒性介导其在携带大MOPC-315肿瘤的无胸腺裸鼠的ACIT中的治疗有效性。此外，通过抗肿瘤免疫和美法仑毒性之间的合作根除大型MOPC-315肿瘤，使无胸腺裸鼠在其次级淋巴器官中的T细胞百分比升高，这些T细胞可能是这些小鼠表现出的持久保护性抗肿瘤免疫的原因。
We have previously shown that spleen cells from BALB/c mice that are in the process of eradicating a large MOPC-315 tumor following low-dose (2.5 mg/kg) melphalan (l-phenylalanine mustard) therapy are effective in preventing tumor progression upon adoptive transfer into BALB/c mice bearing a barely palpable tumor that had been treated with a subcurative dose of melphalan [Mokyr et al. (1989) Cancer Res 49: 4597]. Here we show that such spleen cells in conjunction with a subcurative dose of drug (adoptive chemoimmunotherapy, ACIT) can cause the complete regression of a large (15–20 mm) s.c. MOPC-315 tumor in a large percentage of T-cell-deficient (athymic nude) tumor-bearing mice. Spleen cells that were effective in ACIT of athymic nude mice displayed in vitro a substantial direct lytic activity against MOPC-315 tumor cells, and the lytic activity was greatly enhanced when the spleen cells were cultured for 5 days with or without mitomycin-C-treated MOPC-315 stimulator tumor cells. The cells responsible for the therapeutic effectiveness of the spleen cells in ACIT of athymic nude mice, as well as the cells responsible for the direct in vitro anti-MOPC-315 lytic activity of the spleen cells, were of the Lyt 2 and not the L3T4 phenotype. Most of the athymic nude mice that completely eradicated a large MOPC-315 tumor as a consequence of ACIT were capable of rejecting a challenge with 30–100 times the minimal lethal tumor dose for 100% of normal BALB/c mice administered more than 1 month after the ACIT. The ability of these athymic nude mice to resist the tumor challenge was associated with the presence of a greatly elevated percentage of cells expressing T cell surface markers in their spleens. Thus, it is conceivable that splenic Lyt 2+T cells from melphalan-treated BALB/c mice bearing a large MOPC-315 tumor mediate their therapeutic effectiveness in ACIT of athymic nude mice bearing a large MOPC-315 tumor, at least in part, through direct cytotoxicity for MOPC-315 tumor cells. In addition, eradication of a large MOPC-315 tumor through cooperation between antitumor immunity and melphalan toxicity endues the athymic nude mice with an elevated percentage of T cells in their secondary lymphoid organs, and these T cells are probably responsible for the long-lasting protective antitumor immunity exhibited by these mice.