ACTIVE SPECIFIC IMMUNOTHERAPY WITH VACCINIA COLON ONCOLYSATE ENHANCES THE IMMUNOMODULATORY AND ANTITUMOR EFFECTS OF INTERLEUKIN-2 AND INTERFERON-ALPHA IN A MURINE HEPATIC METASTASIS MODEL
ACTIVE SPECIFIC IMMUNOTHERAPY WITH VACCINIA COLON ONCOLYSATE ENHANCES THE IMMUNOMODULATORY AND ANTITUMOR EFFECTS OF INTERLEUKIN-2 AND INTERFERON-ALPHA IN A MURINE HEPATIC METASTASIS MODEL
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DOI：
10.1007/bf01740939
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发表时间：
1990-08-01
影响因子：
5.8
通讯作者：
WALLACK, MK
中科院分区：
文献类型：
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作者：
ARROYO, PJ;BASH, JA;WALLACK, MK
细胞因子作为主要或辅助抗肿瘤剂的作用已得到充分证实。特别是，白细胞介素-2 (IL-2) 和干扰素在单独给药时已被证明是有效的抗肿瘤药物，并且似乎在根除免疫原性肿瘤的转移方面具有协同作用。病毒肿瘤裂解物形式的主动特异性免疫疗法在癌症治疗中也显示出有效性。考虑到这一点，我们决定将这些药物组合在辅助三联疗法中，并在小鼠结肠癌肝转移模型中比较它们与其他治疗在肿瘤负荷和生存方面的有效性。 BALB/c 小鼠脾内注射 CC-36（一种弱免疫原性小鼠结肠腺癌），以产生人工肝转移。将动物分为一个对照组和七个治疗组，接受痘苗结肠溶瘤物(VCO)、IL-2、干扰素-α。 (IFN.α.)单独使用，或这些药物的组合。跟踪一半动物的存活情况，另一半在实验结束时处死以量化肿瘤负荷。处死动物的血液用于一系列免疫学测试，以证明每个治疗组中外周血淋巴细胞（PBL）的溶细胞潜力，以及表征作为效应细胞的细胞的表型。三辅助疗法组是迄今为止最有效的治疗组，与其他组相比，存活率达到 100%，并且肿瘤负荷显着降低。此外，该组动物的 PBL 显示 CC-36 靶细胞体外裂解率为 69.4%。这些效应淋巴细胞被定性为 ASMG1-/Lyt2.2+ 溶细胞淋巴细胞。我们得出的结论是，这些淋巴细胞受到 VCO 的刺激，并通过三重方案中给予的细胞因子的免疫调节进一步增强，并且这种方案可能对治疗弱免疫原性肿瘤已形成的肝转移有益。
The role of cytokines as primary or adjuvant antineoplastic agents has been well established. Interleukin-2 (IL-2) and the interferons have, particularly, proven to be effective antitumor agents when given alone, and seem to act synergistically on the eradication of metastases from immunogenic tumors. Active specific immunotherapy, in the form of viral oncolysates, has also shown effectiveness in cancer therapy. Bearing this in mind, we decided to combine these agents in an adjuvant triple regimen and compare their effectiveness to other treatments in terms of tumor burden and survival in a murine colon cancer hepatic metastases model. BALB/c mice were injected with CC-36, a weakly immunogenic murine colon adenocarcinoma, intrasplenically, to produce artificial liver metastases. The animals were divided into one control group and seven treatment groups receiving either vaccinia colon oncolysate (VCO), IL-2, interferon-.alpha. (IFN.alpha.) alone, or combinations of these agents. Half the animals were followed for survival and the other half were sacrificed at the end of the experiment for quantification of tumor burden. The blood of the sacrificed animals was utilized in a series of immunological tests in order to demonstrate the cytolytic potential of the peripheral blood lymphocytes (PBL) in each treatment group, as well as to characterize phenotypically the cells acting as effectors. The triple-adjuvant regimen group was by far the most effective treatment group, demonstrating 100% survival and a significant reduction in tumor burden when compared to other groups. Furthermore, the PBL from the animals in this group showed 69.4% lysis of the CC-36 target cells in vitro. These effector lymphocytes were characterized as ASMG1-/Lyt2.2+ cytolytic lymphocytes. We conclude that these lymphocytes were stimulated by the administration of VCO and further augmented by the immunomodulation of the cytokines given in the triple regimen, and that such a regimen might prove beneficial in the treatment of established hepatic metastases from weakly immunogenic tumors.