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Cancer Immunol Res:疫苗Tecemotide与顺铂联合有望延长癌症患者生存期

来源:生物谷 2014-03-22 13:45

2014年3月23日讯 /生物谷BIOON/--近日,加州大学戴维斯分校研究人员发现,肺癌疫苗Tecemotide当与化疗顺铂联合使用,能刺激免疫应答,降低小鼠肺癌肿瘤的数量。该研究还发现,放射治疗并不会没显著损害免疫应答。该论文发表在杂志Cancer Immunology Research上。

虽然Tecemotide(也被称为Stimuvax),显示出巨大的潜力,但近期III期临床试验发现其对患小细胞肺癌(NSCLC)患者没有整体的生存益处。然而,进一步的分析表明,一组病人在给予Tecemotide后接受同步放化疗和放疗,会确实受益于疫苗。因此,Tecemotide的制造商默克赞助额外的动物和人类研究,以希望获得良好结果。

加州大学戴维斯分校教授Michael DeGregorio说:我们正在试图将Tecemotide作为一个潜在的维持治疗药物,以延长生存期和提高生活质量。Tecemotide通过靶向MUC1蛋白(这是经常在肺癌,乳腺癌,前列腺癌和其它癌症过度表达的蛋白)激活免疫应答。疫苗刺激机体产生干扰素γ和靶向MUC1的杀伤性T淋巴细胞,杀伤T淋巴细胞找出癌细胞和摧毁MUC1癌细胞。

团队想知道顺铂/Tecemotide治疗,同时配合放射治疗是否可以提高免疫反应和改变肺癌轨迹,稳定病情。这项研究产生了一些积极的结果,Tecemotide增加干扰素γ的水平,并增强了T细胞对MUC1表达癌细胞的应答。Tecemotide及顺铂两者都降低了肺癌肿瘤数量。然而, Tecemotide及顺铂组合疗法增强各自影响,这表明Tecemotide增加顺铂的抗癌活性。

虽然放射疗法确实降低淋巴细胞的数量,但它并未表现出阻碍免疫反应。此外,放射治疗数小时后干扰素水平反而增加了。辐射实际上可能有助于暴露疫苗的靶标,DeGregorio说:我们认为这疫苗可能与标准治疗耦合创造一个维持治疗方法,如果我们能够帮助生存期为18至20个月患者延长至30个月或以上的寿命,这将会带来很大的好处。(生物谷Bioon.com)

 

doi:10.1158/2326-6066.CIR-13-0205
Antitumor Effects of Cisplatin Combined with Tecemotide Immunotherapy in a Human MUC1 Transgenic Lung Cancer Mouse Model

Chiao-Jung Kao, Gregory T. Wurz1, Arta Monjazeb, Daniel P Vang, Timothy B Cadman, Stephen M. Griffey, Michael Wolf, and Michael W DeGregorio,*

The goals of the present study were to: (1) define the effects of simultaneous cisplatin/ tecemotide therapy on tumor development in a human mucin 1 (MUC1) transgenic lung cancer mouse model; and (2) examine the effects of radiation therapy (RTX) on splenocytes, serum cytokines, and immune response to tecemotide. Two hundred twenty-six human MUC1 transgenic mice were used in five studies designed to assess: (1) serum cytokine and immune responses following four weekly 10-μg doses of tecemotide; (2) effects of simultaneous administration of cisplatin (2.5 mg/kg x 2 doses/cycle x 4 cycles) and tecemotide (2 cycles x 8 weekly 10-μg doses/cycle) therapy on tumor development, serum cytokines and immune response; (3) dose response effects of RTX on lymphocyte counts 16 h following doses of 2-8 Gy; (4) time course of lymphocyte recovery from 16 h to 20 d following 8 Gy RTX; and (5) effects of simultaneous administration of RTX (8 Gy) and tecemotide on immune response to tecemotide (4 weekly 10-μg doses). Serum cytokines were analyzed by multiplex immunoassay, interferon gamma (IFN-γ) immune responses by ELISpot, and lung tumor foci by lung whole mounts. Simultaneous cisplatin/tecemotide therapy resulted in significant and additive reduction in lung tumor foci compared to control mice, with significantly elevated serum IFN-γ levels and specific IFN-γ immune responses observed in both tecemotide and tecemotide + cisplatin treated mice. Finally, neither cisplatin nor radiation interfered with the immune response to tecemotide.

 

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