Fujimaki W, Itoh K, An T, Gano J B, Ross M I, Mansfield P F, Balch C M, Augustus L B, Karkevitch D D, Johnston D
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Cancer Biother. 1993 Winter;8(4):307-18. doi: 10.1089/cbr.1993.8.307.
We conducted a pilot study using liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) preoperatively in patients with stage III or IV resectable melanoma who were at high risk for recurrence. Patients received L-MTP-PE for 1 month before surgery and then 5 months postoperatively. Several immune parameters were monitored during preoperative therapy to search for correlations with clinical (tumor) response. The 18 patients were classified into three groups according to their responses and disease-free intervals: no evidence of disease (NED) at week 24 of therapy, relapse during therapy and progressive disease on therapy noted at the time of surgery. Six of nine patients in the NED group demonstrated increased monocyte tumoricidal activity (MTA) during week 1 of therapy. MTA increased in three of the six patients in the relapse group. MTA did not increase in the three patients who had progressive disease on therapy. Plasma neopterin levels were elevated by 72 h following the first L-MTP-PE dose in all 18 patients. Circulating levels of tumor necrosis factor were elevated in 15 of 16 patients tested, and IL-6 levels were elevated in all 18 patients. Melanoma cells from all three patients with progressive disease at the time of surgery proliferated well in vitro, whereas tumor cells from 10 of the 15 patients in the other two groups did not proliferate. There were no discernible differences among the three groups in the magnitude of IL-2-induced proliferation of tumor infiltrating lymphocytes. However, IL-2-activated TILs from the NED group exhibited cytotoxicity against autologous tumor cells in vitro. In summary, whereas L-MTP-PE stimulated several immunologic responses in all patients, the only two parameters that correlated with clinical status were MTA and the tumor proliferation assay. These two biologic assays could serve to distinguish potential responders from nonresponders early in the course of treatment.
我们进行了一项初步研究，对III期或IV期可切除的黑色素瘤且复发风险高的患者术前使用脂质体包裹的胞壁酰三肽磷脂酰乙醇胺（L-MTP-PE）。患者在手术前接受L-MTP-PE治疗1个月，术后再接受5个月治疗。在术前治疗期间监测了几个免疫参数，以寻找与临床（肿瘤）反应的相关性。根据患者的反应和无病间期，将18例患者分为三组：治疗第24周时无疾病证据（NED）组、治疗期间复发组和手术时记录为治疗中疾病进展组。NED组9例患者中有6例在治疗第1周时单核细胞杀瘤活性（MTA）增加。复发组6例患者中有3例MTA增加。治疗中疾病进展的3例患者MTA未增加。所有18例患者在首次给予L-MTP-PE剂量后72小时血浆新蝶呤水平升高。检测的16例患者中有15例循环肿瘤坏死因子水平升高，所有18例患者IL-6水平均升高。手术时疾病进展的3例患者的黑色素瘤细胞在体外增殖良好，而其他两组15例患者中有10例的肿瘤细胞未增殖。三组间IL-2诱导的肿瘤浸润淋巴细胞增殖幅度无明显差异。然而，NED组经IL-2激活的肿瘤浸润淋巴细胞在体外对自体肿瘤细胞表现出细胞毒性。总之，虽然L-MTP-PE在所有患者中均刺激了几种免疫反应，但与临床状态相关的仅有的两个参数是MTA和肿瘤增殖试验。这两种生物学检测方法可在治疗过程早期区分潜在的反应者和无反应者。
