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Bavituximab可能加强肺癌放射线治疗效果

来源:医源世界 作者:Allison Gandey 2008-1-4
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摘要: 早期的研究指出,放射线疗法加上一种实验用药bavituximab可以改善肺癌的治疗效果。Bavituximab是Peregrine药厂正在研发的一种嵌合性抗磷酸丝氨酸单株抗体,目前于美国与印度的临床试验中检验其对抗固体癌症的效果,也正开发作为病毒治疗药物。在这项最新的研究中,一种发表于9月1日临床癌症研究期刊的动物模式,研究者证......


  早期的研究指出,放射线疗法加上一种实验用药bavituximab可以改善肺癌的治疗效果。Bavituximab是Peregrine药厂正在研发的一种嵌合性抗磷酸丝氨酸单株抗体,目前于美国与印度的临床试验中检验其对抗固体癌症的效果,也正开发作为病毒治疗药物。
  
  在这项最新的研究中,一种发表于9月1日临床癌症研究期刊的动物模式,研究者证实bavituximab合并放射线治疗可以加强疗效。
  
  资深作者、达拉斯德州大学西南医学中心药理学科Philip Thorpe博士在一篇新闻稿中表示,大约有30%的肺癌患者接受放射线治疗,且在肺癌的动物模式中,我们发现这个单株抗体改善放射线治疗的疗效,且没有看到其他化学治疗药物的毒性;这是个双赢的局面。
  
  Thrope博士是Peregrine药厂的顾问,持有该公司股份。
  
  他附带表示,虽然目前对肺癌有许多治疗方法,但5年存活率仍然仅有15%,这告诉我们必须立即研发新的治疗策略。
  
  在与Medscape的访谈中,Thorpe博士表示,如果他需要接受放射线治疗,他将会希望加上bavituximab;血管标靶药物,如bavituximab,被认为可以杀死肿瘤且不会对周边健康组织造成伤害;不但如此,该药物相较于摧毁快速分裂正常以及癌症细胞的传统治疗,造成不良反应的机率较低。
  
  【探索新合并疗法的临床研究即将展开】
  在这项新研究中,研究者针对对放射线有抵抗性的A549人类肺癌细胞无毛鼠进行研究,他们以免疫萤光染色法分析放射线引发内皮细胞以及A549肿瘤细胞暴露于磷酸丝氨酸之下;该研究团队以组织学、与抗体独立细胞调控细胞毒性实验,检验增强抗肿瘤效果的机转。
  
  Thorpe医师与其同事发现,对人类肺癌异种移植进行局部放射线治疗,增加肿瘤血管暴露在磷酸丝氨酸的比例,从4%增加到26%;Bavituximab与放射线治疗抑制肿瘤细胞生长达80%,且比单独进行放射线治疗或使用bavituximab有效(P<0.01)。
  
  他们报告合并治疗降低血管密度且增加单核球浸润进肿瘤团块中,超出单独治疗。
  
  研究者的结论是,目前这项研究显示,应该考虑进行肺癌、与其他经常需要接受放射线治疗之癌症病患使用bavituximab合并放射线的临床评估。
  
  Thrope博士表示,他期待早日进行使用合并bavituximab与放射线治疗的研究。
  
  目前这项研究由Gillson Longenbaugh基金会以及安德森基金会赞助,且与加州塔斯丁Peregrine药厂有一项赞助研究协议,这项研究也由一项来自美国癌症学会的博士后研究计划赞助。

Bavituximab May Boost Radiation in Lung Cancer

 

By Allison Gandey
Medscape Medical News

Early results are pointing to the benefit of adding the experimental drug bavituximab to radiation to improve therapeutic benefit in lung cancer. Bavituximab is a chimeric antiphosphatidylserine monoclonal antibody under development by Peregrine Pharmaceuticals, currently being tested in clinical trials in the United States and India for its effectiveness against solid tumor cancers and also being explored in the treatment of viral infections.

In this latest study, a mouse model published in the September 1 issue of Clinical Cancer Research, investigators show that bavituximab combined with radiation therapy boosts efficacy.

"About 30% of all lung cancer patients receive radiation, and, in this animal model of lung cancer, we found that this monoclonal antibody improves the efficacy of radiation therapy without the toxicity seen in other chemotherapeutic drugs," senior author Philip Thorpe, PhD, from the department of pharmacology at the University of Texas Southwestern Medical Center, in Dallas, said in a news release. "It’s a win-win."

Dr. Thorpe is a consultant for Peregrine Pharmaceuticals and reportedly has an equity interest in the company.

Although there are current lung cancer therapies, the 5-year survival rate remains at only 15%, he added. "This tells us that there is an urgent need to develop new treatment strategies."

During an interview with Medscape, Dr. Thorpe said that if he required radiation for his own treatment, he would want to have bavituximab added. Vascular targeting agents such as bavituximab are said to kill tumors without causing damage to surrounding healthy tissue. And they cause fewer adverse effects than conventional therapies that destroy rapidly dividing normal cells along with the cancer cells.

Clinical Trials Exploring New Combination to be Launched

In this new study, investigators looked at nude mice with radiation-resistant A549 human lung tumors. They analyzed radiation-induced phosphatidylserine exposure on endothelial cells and A549 tumor cells using immunofluorescence staining. The research team examined the mechanism of the enhanced antitumor effect by histology and antibody-dependent cell-mediated cytotoxicity experiments.

Dr. Thorpe and colleagues found that focal irradiation of the human lung cancer xenografts increased the percentage of tumor vessels with exposed phosphatidylserine from 4% to 26%. Bavituximab and radiation inhibited tumor growth by 80% and were superior to radiation therapy or bavituximab alone (P < .01).

They report that the combination therapy reduced blood vessel density and enhanced monocyte infiltration into the tumor mass beyond that observed with individual treatments.

The researchers conclude, "The present study suggests that clinical evaluation of bavituximab in combination with radiation therapy should be considered for lung cancer patients and patients with other cancers commonly treated with radiation therapy."

Dr. Thorpe said he expects new clinical trials using a combination of bavituximab and radiation therapy to start soon.

The present study was supported by the Gillson Longenbaugh Foundation and the Anderson Foundation, a sponsored research agreement with Peregrine Pharmaceuticals Inc, in Tustin, California. The work was also supported by a postdoctoral fellowship from the American Cancer Society.

Clin Cancer Res. 2007;13:5211-5218. Abstract


 


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