用MALP-2的免疫疗法可抑制小鼠模型的胰腺癌
发布于 2004-03-08 · 浏览 824 · IP 湖北湖北
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路透社2004年3月4日纽约讯
据3月《肠》杂志（Gut 2004;53:355-361）上的一篇报告说，小鼠胰腺癌模型用巨噬细胞活化脂肽2 (MALP-2)行免疫治疗，可以抑制肿瘤。下月，研究者将开始早期临床试验。
作者、德国海德堡大学的马顿（Angela Maerten）和同事解释，MALP-2激活了核转录因子kappaB，引起多种细胞因子和化学增活素合成和树状突细胞的突变，在体外试验中有抗肿瘤活性。为此，他们检查了MALP-2对小鼠胰腺癌模型的抗癌能力。
结果表明，MALP-2显著减少了皮下的肿瘤生长，平均生存时间从18-19天延长到23天。对有确定性原位肿瘤的小鼠，MALP-2腹膜内治疗将平均生存时间从16天延长到20天，瘤体内注射从平均19天延长到26天。加用吉西他滨治疗显著延长了平均生存期，从29天增到37天。流式细胞术分析证实，细胞毒性T细胞和自然杀伤(NK)细胞数增加。组织学研究表明MALP-2治疗后肿瘤进行性坏死，没有淋巴细胞浸润。
“我们4月将开始在海德堡大学外科招募病人来参加I/II临床试验”，马顿告诉路透社记者，“15人将瘤体注射一次20µg MALP-2，并加大剂量。然后2周后还要接受标准的吉西他滨化疗”。“免疫系统的广泛激活可能打破肿瘤引起的免疫抑制，也许能控制肿瘤”。“我相信MALP-2可能以同样的方式作用于其它肿瘤”，他补充，“既然它通过激活内在的免疫系统来起作用，我们就不能指望它可以用于缺乏MHC的肿瘤”。
Tumour suppression induced by the macrophage activating lipopeptide MALP-2 in an ultrasound guided pancreatic carcinoma mouse model
Background and aim: Carcinoma of the exocrine pancreas has a particularly poor prognosis. Therefore, novel therapeutic strategies such as immunotherapy are required. Here we investigated the immunomodulatory capacity of macrophage activating lipopeptide 2 (MALP-2), which binds to toll-like receptors 2 and 6 and induces activation of nuclear factor B in monocytes. This causes the release of early stage leucocyte attracting chemokines and proinflammatory cytokines.
Methods: MALP-2 was tested in a new orthotopic ultrasound guided pancreatic cancer mouse model. This model is close to the biological situation and avoids the stress and immunostimulation caused by laparotomy. Cells from the syngeneic, highly aggressive, and metastatic cell line Panc 02 were administered orthotopically, by ultrasound guidance, to C57bl/6 mice. MALP-2 was administered intratumorally or intraperitoneally and tumour growth, immune status, and leucocyte infiltration at the tumour site were determined.
Results: We showed a tumour suppressive effect induced by a single injection of MALP-2. Median survival increased from 21 to 30 days (p<0.002). Combining chemotherapy (gemcitabine) with MALP-2 treatment caused further prolonged survival (median survival 27 days with chemotherapy alone v 37 days for combined treatment; p<0.0002). The life prolonging effect was paralleled by a significant increase in cytotoxic T cells, restoration of ß2 integrin expression on lymphocytes, and high expression of CD45RB on T helper cells. Immunohistochemical stains showed strong cytotoxic T lymphocyte and natural killer cell infiltration.
Conclusions: In conclusion, in a model of orthotopic pancreatic cancer in mice, we induced a tumour suppressive effect by treatment with a synthetic lipopeptide. Treatment with MALP-2 could be an option for immunotherapy in pancreatic cancer.
Gut 2004;53:355-361
原文如下！！！
据3月《肠》杂志（Gut 2004;53:355-361）上的一篇报告说，小鼠胰腺癌模型用巨噬细胞活化脂肽2 (MALP-2)行免疫治疗，可以抑制肿瘤。下月，研究者将开始早期临床试验。
作者、德国海德堡大学的马顿（Angela Maerten）和同事解释，MALP-2激活了核转录因子kappaB，引起多种细胞因子和化学增活素合成和树状突细胞的突变，在体外试验中有抗肿瘤活性。为此，他们检查了MALP-2对小鼠胰腺癌模型的抗癌能力。
结果表明，MALP-2显著减少了皮下的肿瘤生长，平均生存时间从18-19天延长到23天。对有确定性原位肿瘤的小鼠，MALP-2腹膜内治疗将平均生存时间从16天延长到20天，瘤体内注射从平均19天延长到26天。加用吉西他滨治疗显著延长了平均生存期，从29天增到37天。流式细胞术分析证实，细胞毒性T细胞和自然杀伤(NK)细胞数增加。组织学研究表明MALP-2治疗后肿瘤进行性坏死，没有淋巴细胞浸润。
“我们4月将开始在海德堡大学外科招募病人来参加I/II临床试验”，马顿告诉路透社记者，“15人将瘤体注射一次20µg MALP-2，并加大剂量。然后2周后还要接受标准的吉西他滨化疗”。“免疫系统的广泛激活可能打破肿瘤引起的免疫抑制，也许能控制肿瘤”。“我相信MALP-2可能以同样的方式作用于其它肿瘤”，他补充，“既然它通过激活内在的免疫系统来起作用，我们就不能指望它可以用于缺乏MHC的肿瘤”。
Tumour suppression induced by the macrophage activating lipopeptide MALP-2 in an ultrasound guided pancreatic carcinoma mouse model
Background and aim: Carcinoma of the exocrine pancreas has a particularly poor prognosis. Therefore, novel therapeutic strategies such as immunotherapy are required. Here we investigated the immunomodulatory capacity of macrophage activating lipopeptide 2 (MALP-2), which binds to toll-like receptors 2 and 6 and induces activation of nuclear factor B in monocytes. This causes the release of early stage leucocyte attracting chemokines and proinflammatory cytokines.
Methods: MALP-2 was tested in a new orthotopic ultrasound guided pancreatic cancer mouse model. This model is close to the biological situation and avoids the stress and immunostimulation caused by laparotomy. Cells from the syngeneic, highly aggressive, and metastatic cell line Panc 02 were administered orthotopically, by ultrasound guidance, to C57bl/6 mice. MALP-2 was administered intratumorally or intraperitoneally and tumour growth, immune status, and leucocyte infiltration at the tumour site were determined.
Results: We showed a tumour suppressive effect induced by a single injection of MALP-2. Median survival increased from 21 to 30 days (p<0.002). Combining chemotherapy (gemcitabine) with MALP-2 treatment caused further prolonged survival (median survival 27 days with chemotherapy alone v 37 days for combined treatment; p<0.0002). The life prolonging effect was paralleled by a significant increase in cytotoxic T cells, restoration of ß2 integrin expression on lymphocytes, and high expression of CD45RB on T helper cells. Immunohistochemical stains showed strong cytotoxic T lymphocyte and natural killer cell infiltration.
Conclusions: In conclusion, in a model of orthotopic pancreatic cancer in mice, we induced a tumour suppressive effect by treatment with a synthetic lipopeptide. Treatment with MALP-2 could be an option for immunotherapy in pancreatic cancer.
Gut 2004;53:355-361
原文如下！！！
最后编辑于 2004-03-08 · 浏览 824
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