肿瘤细胞在生长分裂的过程中，必须经由血管透过源源不绝的血液，提供足够的养份，因此绝大多数的癌细胞表面，都存在着吸引血管上皮生长因子 (vascular endothelial growth factor；简称 VEGF)的受体蛋白，因此科学家就利用着这个特点，设计出可能成为抗癌武器的新一代药物。
这次由美国德州大学 M.D.安德逊癌症中心的科学家所参与的研究计划，利用上述癌细胞的特性 开发出一种融合分子，据了解这个分子主要是由一个最小的VEGF蛋白质，黏附著称为 gelonin的毒性分子，研究人员想利用癌细胞会吸附 VEGF蛋白质的特性，将毒性分子拉近，完成毒杀癌细胞的作用。
参与计划的科学家，利用恶名昭彰的前列腺癌细胞 (prostate cancer cells)，注射到实验动物模型的小鼠骨髓中，再透过上述的融合分子加以治疗，结果移殖癌细胞的小鼠，在提供融合分子的实验组中，居然没有任何恶性肿瘤的踪迹，可见的这个抗癌的融合分子，确实具有毒杀癌细胞的功效。
英文原文：
‘Trojan Horse’ Technology Destroys Blood Supply to Cancer Tumors in Mice
Researchers at M. D. Anderson and The University of Texas Southwestern Medical Center at Dallas have demonstrated in mice that a new drug formed by linking a vascular endothelial growth factor to a toxin will target and destroy the blood vessels supplying a malignant tumor.
Dr. Michael Rosenblum, professor of medicine at M. D. Anderson, said tests of VEGF121/rGelonin (VEGF/rGel) in mice demonstrated it could selectively destroy blood vessels supplying human solid tumors without harming the vasculature of normal tissue.
“This is like a ‘Trojan horse’ approach to kill the blood vessels that supply solid tumors. We’re using the vascular endothelial growth factor (VEGF) as a carrier to deliver a toxic agent selectively to the tumor’s blood supply – in effect, starving the tumor,” said Dr. Rosenblum, senior author of the study.
The research, which is in the June 11 Proceedings of the National Academy of Sciences, was the result of an ongoing collaboration between UT Southwestern and M. D. Anderson. VEGF/rGel was designed jointly and developed at M. D. Anderson and UT Southwestern.
For the study, mice were injected with human melanoma and human prostate cancer cells. The research showed that tumor growth in the mice that received VEGF/rGel was reduced to 16% of the untreated mice, said Dr. Philip Thorpe, Professor of Pharmacology, who directed tests of VEGF/rGel at UT Southwestern with Dr. Sophia Ran, Assistant Professor of Pharmacology. Both are affiliated with the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.
“The anti-tumor effects of the VEGF/rGel fusion construct against both melanoma and human prostate cancer in mouse models was impressive in magnitude and prolonged,” Dr. Thorpe said. “These studies suggest that VEGF/rGel has potential as an anti-tumor agent for treating cancer patients.”
A clinical trial to test the new technique in patients is expected to begin within the year at M. D. Anderson, Dr. Rosenblum said.
“The significance of this fusion toxin is that it’s not specific to one kind of tumor – it has impressive anti-tumor effects in various kinds of tumors – including melanoma and prostate cancers,” Dr. Rosenblum said. “We need additional research to determine if it is equally effective in other cancers.”
In the mouse study, destruction of the tumor blood vessels was observed as early as 48 hours after administration of the VEGF/rGel. There was no visible damage in any normal organs, including the kidneys, of the treated mice, Dr. Rosenblum said.
VEGF is one of the predominant factors responsible for angiogenesis – the ability of a tumor to create new blood vessels to maintain growth and metastasize.
The researchers chose the genetically engineered toxin gelonin to link to the VEGF “carrier” because it does not appear to be antigenic in human clinical trials conducted thus far at M. D. Anderson, and it does not cause damage to normal blood vessels as do other toxins that have been explored for use in anti-tumor therapies, Dr. Rosenblum said.
Genetically engineered gelonin was developed in a research program at M. D. Anderson, and related intellectual property rights are owned by Research Development Foundation (RDF). RDF is in the process of licensing the gelonin technology for use with various cell-targeting proteins such as growth factors and antibodies.
Therapies that attack tumor blood vessels have recently been a hot area in cancer research because they appear to bypass the major problem with chemotherapy – the tumor cells’ ability to mutate and develop resistance to the drugs.
Other researchers from M. D. Anderson who contributed to the work were Liesbeth M. Veenendaal, Lawrence Cheung, Nora Navone, and Hangqing Jin. The Med. Klinik und Poliklinik der Universität Ulm in Germany also contributed to the research. The work was supported in part by the University of Utrecht and the Dutch Cancer Foundation, Koningen Wilhelmina Funds, the National Institutes of Health and Arcus Therapeutics.
