马上注册登录,享用更多感控资源,助你轻松入门。
您需要 登录 才可以下载或查看,没有账号?注册
|
×
Fighting cancer with light-activated antibodies
Date released 30 October 2007
Scientists at Newcastle University have developed a cancer fighting technology which uses ultra-violet light to activate antibodies which very specifically attack tumours.
Therapeutic antibodies have long been recognised as having excellent potential but getting them to efficiently target tumour cells has proved to be very difficult.
Now, Professor Colin Self and Dr Stephen Thompson from Newcastle University have developed a procedure to cloak antibodies which can then be activated by UV-A light and so can be targeted to a specific area of the body just by shining a probe at the relevant part.
This procedure maximizes the destruction of the tumour while minimising damage to healthy tissue.
Professor Self says, “I would describe this development as the equivalent of ultra-specific magic bullets. This could mean that a patient coming in for treatment of bladder cancer would receive an injection of the cloaked antibodies. She would sit in the waiting room for an hour and then come back in for treatment by light. Just a few minutes of the light therapy directed at the region of the tumour would activate the T-cells causing her body’s own immune system to attack the tumour.“
The details are contained in two papers published online today in the journal ChemMedChem.
The Newcastle University researchers demonstrate in the first paper the procedure of coating the surface of a protein, such as an antibody, with an organic oil which is photocleavable, a process called “cloaking”. This prevents the antibody reacting within the body unless it is illuminated.
When UV-A light is shone onto the cloaked antibody it is activated. The activated antibody binds to T-cells, the body’s own defence system, triggering the T-cells to target the surrounding tissue.
In the second paper, they demonstrate that when the cloaked antibodies are activated by light near a tumour, the tumour is killed. This work means that antibodies can be targeted to kill cancer tumours with much greater specificity giving fewer side effects.
These cloaked antibodies can be used alone, or in conjunction with the many antibodies already produced against a wide variety of cancers as bispecific complexes. These complexes are formed from two antibodies, one antibody binds to a tumour marker, the other with a T-cell. The T-cell binding end remains inactive until re-activated by light. This means when the bispecific antibody binds to healthy tissues away from light, it cannot activate T-cells, resulting in far fewer side effects.
Professor Self says, “This opens up so many possible applications for example, for patients who are undergoing surgery for prostate cancer. After the surgeon has removed the bulk of a tumour, the patient could then be injected with bispecific antibodies and a light shone at the affected area which would target the patient’s own immune system to the tumour site.
“This is therefore a very specific treatment and while our work indicates that sunlight doesn’t activate these antibodies, patients may have to be advised to avoid direct sunlight for a short period after treatment.”
BioTransformations Ltd, the company set up by Professor Colin Self to develop the technology, is looking to begin clinical trials on patients with secondary skin cancers in early 2008.
纽卡斯尔大学的科学家开发了一种对抗癌症的新技术,这种技术是用紫外光激活能特异性攻击肿瘤的抗体。
治疗性抗体早就被认为具有极好的潜力,但是要用他们来有效的瞄准肿瘤细胞已经被证实非常的困难。
现在,纽卡斯尔大学的Colin Self教授和 Dr Stephen Thompson发展了一项程序以掩饰抗体,这种抗体能被UV-A紫外光激活,因此能瞄准由荧光探针标记发光的身体的特定区域。
这项程序能最大限度的毁坏肿瘤而且减小对健康组织的损坏。
Self教授说:“我们把这项技术描述成相当于具有超特异性的魔术子弹,这意味着因膀胱癌而治疗的病人会接受一种隐匿型抗体的注射,她坐在等候室里等一小时,然后再用光治疗。用光直接对准肿瘤区域几分钟就会激活T细胞促使她的自身免疫系统攻击肿瘤。”
今天刊登在ChemMedChem杂志网页上的两篇论文包括了这种程序的详细过程。
纽卡斯尔大学的研究人员在第一篇论文中描述了包被蛋白程序的过程,如抗体,用一种具有光裂性的有机油包裹,这个过程叫做“隐匿”。这样在没有光照的情况下能防止抗体和机体反应。
当UV-A紫外光照射在包好的抗体上时,抗体被激活。激活的抗体结合T细胞,机体的自身防御系统触发T细胞靶向周围的组织。
在第二篇研究论文中,他们显示了当包被的抗体被肿瘤附近的光激活的时,肿瘤被杀死。这个作用意味着抗体能靶向杀死癌症肿瘤,并有更高的特异性更少的副作用。
这些隐匿的抗体可单独用,或联合多种已经生产的对抗各种癌症的抗体作为双功能复合体。这种复合体由两种抗体组成,一种抗体结合一个肿瘤标记物,另一种抗体结合T细胞。T细胞结合末端保持无活性状态直到被光重新激活。这就是说,当双功能抗体与远离光线的健康组织结合时,它不会激活T细胞,这样就极少由副作用。
Self教授说:“这开辟了许多可能的应用,以正在经历手术的前列腺癌病人为例。手术移出肿块后,给病人注射双功能抗体和用光照射易受影响的区域,这个区域能使病人自身免疫系统靶向肿瘤位点。”
因此,这是一个很有特异性的治疗,同时,我们的研究显示阳光不能够激活这些抗体,在治疗后的很短一段时期内,可能会建议病人避免阳光的直接照射。
由Colin Self教授建立的BioTransformations有限公司专门用以发展这项技术,该公司有望在2008年初开始对继发性皮肤癌病人进行临床试验。 |