“通用”癌症疫苗：可攻击90%的癌细胞，有望2020上市 - 干细胞行业新闻干细胞之家



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发表于 2012-4-22 18:03 |只看该作者 |倒序浏览 |打印

                           第一篇：PNAS：癌症“万能疫苗”时间：2011年12月16日来源：生物通6 Y2 E% H9 e; j1 V, d7 e1 w
生物通报道：随着FDA近期批准了首支治疗性癌症疫苗，癌症研究进入了疫苗研发的新纪元，近期来自梅奥诊所医学院，佐治亚大学的研究人员发表了题为“Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine”的文章，首次开发出利用免疫系统按照蛋白不同的糖结构，识别和杀死癌细胞的疫苗，这种疫苗能对抗70%的癌症，是目前所得到的最广泛的癌症预防疫苗，相关成果公布在PNAS杂志上。
文章的通讯作者是佐治亚大学癌症中心的Geert-Jan Boons教授，以及梅奥诊所的Sandra J. Gendler教授，Boons教授表示，“这种疫苗引起了一个高强度的免疫反应，能够激活免疫系统3大要素，缩减肿瘤的大小平均80%左右”。
随着FDA近期批准首支治疗性癌症疫苗——用于治疗前列腺癌的Provenge，以及预防性疫苗在临床实验中的好消息，代表着我们正在进入癌症疫苗研发的新纪元。这项最新的疫苗成果证明能用于小鼠的乳腺癌，前列腺癌、胰腺癌、肠癌和卵巢癌，虽然小鼠试验还不能直接在人体发挥治疗作用，但是因为这种疫苗的强度和独特作用方式，还是让研究人员充满希望。
这种疫苗的不同之处在于其利用的是免疫系统对抗肿瘤——一般疫苗主要是针对癌细胞，这种疫苗通过培养免疫系统，攻击表面带有Muc1蛋白的癌细胞，发挥消灭肿瘤的作用。之前的研究表明MUC1蛋白在超过70%最具侵略性和致命性的癌症上都被发现过，包括大部分的乳腺癌，胰腺癌，卵巢癌和多发性骨髓瘤。
这种特性使得这种疫苗大大优于癌症病人目前常常使用的其他药物，比如当前市场上的“万灵药”赫赛汀，因为目前市售的抗癌药或多或少都会伤害健康的体细胞，有些药物不仅消灭不了癌细胞还会伤害破坏健康体细胞。  & ~5 T/ R7 R( E9 u3 y+ v
通过靶定Muc1蛋白，研究人员就靶定了癌细胞特殊的糖结构，从而激活免疫系统，一旦发现癌细胞，大量抗体就会包围它们，并最终将其消灭，这种利用免疫系统识别出癌细胞的方法，能有效的分别癌细胞与正常细胞，定位后吞噬，更有效，特异性也更强。
从结构上来说，这种疫苗也具有独特性，它是由三部分组成，能分别激活免疫系统的三个组成部分，研究人员发现Muc1蛋白表达的乳腺癌患者中会出现所谓的三阴性”(triple-negative)，也有MUC1蛋白质超表达(overexpressed)问题，一些激素疗法，比如他莫昔芬(Tamoxifen)，芳香化酶抑制剂(Aromatase inhibitors)或抗癌药物赫赛汀(Herceptin)对三阴性乳癌都无效，而这种疫苗也许能通过激活免疫系统的多个部分，有效的控制此类病患病情。
目前研究人员正在积极进行人体实验，希望能在后年获得人体试验的新成果，并于2020年将该疫苗推出市场。8 t% ?2 S4 j) D6 |2 f% ^$ J+ }
原文求高人下载：Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine9 C0 `1 j. Q" L$ X
http://www.pnas.org/content/early/2011/12/13/1115166109.abstract1 b  K0 E5 ]/ r9 i+ i2 d0 Z
                           每日邮报原文：New super vaccine could tackle 70% of lethal cancers and is better than 'wonder drug' Herceptin
A vaccine that could deal a serious blow to seven in ten lethal cancers has been developed by scientists.5 U* k. h. \4 u9 O3 H( r
In tests, it shrunk breast tumours by 80 per cent, and researchers believe it could also tackle prostate, pancreatic, bowel and ovarian cancers.. h( K  t6 U; p( Z# s! w
Even tumours that resist treatment with the best medicines on the market, including the ‘wonder drug’ Herceptin, may be susceptible to the vaccine., r3 D" ~1 W) T7 p+ ~

The experiments done so far have been on mice, but researchers hope to pilot  the drug on people within two years.
If all goes well, the vaccine – one of the first to combat cancer – could be on the market by 2020.  U$ _. N0 @, t: L9 y
More than 300,000 cases of cancer are diagnosed in Britain each year and the disease kills around half this number annually.
Rather than attacking cancer cells, like many drugs, the new treatment harnesses the power of the immune system to fight tumours.5 b# R" [7 Q! u. R- P7 [" Z% d  V+ K+ y! d
The search for cancer vaccines has until now been hampered by fears that healthy tissue would be destroyed with tumours.* }  s, E3 X  |$ S5 ]6 a

To get round this, researchers from the University of Georgia and the Mayo Clinic in the United States focused on a protein called MUC1 that is made in bigger amounts in cancerous cells than in healthy ones.
Not only is there more of it, but a sugar that it is ‘decorated’ with has a  distinctive shape.+ p( M% v" W. J5 r6 P
The vaccine ‘trains’ the immune system to recognise the rogue sugar and turn its arsenal against the cancer.
Researcher Professor Sandra Gendler said: ‘Cancer cells have a special way of thwarting the immune system by putting sugars on the surface of tumour cells so they can travel around the body without being detected.
‘To enable the immune system to recognise the sugar, it took a special vaccine that had three parts to it.
‘That turned out to be a winning combination.’- i2 b, p8 u6 T& Y% C5 r

Her co-author Professor Geert-Jan Boons said: ‘This vaccine elicits a very strong immune response.
‘It activates all three components of the immune system to reduce tumour size by an average of 80 per cent.’$ v# a' a2 m+ o
The misshaped MUC1 sugar is found in 90 per cent of breast and pancreatic cancers and around 60 per cent of prostate cancers, as well as many other tumours.
The researchers believe more than 70 per cent of all cancers that kill may be susceptible to the vaccine.
Despite their excitement, the work is still only at an early stage.
After the ‘dramatic’ results of the tests on mice with breast tumours, the researchers now plan to try the drug on human cancer cells in a dish.
Years of large-scale human trials would need to follow before the drug was judged safe and effective for widespread use in hospitals.* L& h, c% ]5 U+ a- P, r
It could then be used with existing drugs to boost treatment and given to prevent tumours from coming back after surgery.1 X" k- N$ S" V! s
Men and women known to be at high risk of cancer because of their genes could also be vaccinated in an attempt to stop tumours from appearing.
Dr Boons, who has founded a biotech company to commercialise the vaccine, said: ‘We are beginning to have therapies that can teach our immune system to fight what is uniquely found in cancer cells.
‘When combined with early diagnosis, the hope is that one day cancer will become a manageable disease.’
The drug is one of several treatments in the pipeline that work by triggering the immune system to attack and kill cancer cells.! Z5 c) n, s+ G
Dr Caitlin Palframan, of Breakthrough Breast Cancer, said: ‘This exciting  new approach could lead to treatments for breast cancer patients who have few options.
‘It also opens up the possibility of vaccinating high-risk women against breast cancer in the future.
‘However, we need to see this approach trialled in cancer patients before we know its full potential.’: @) h6 I6 N5 ]% P& h$ a0 V
Oliver Childs, of Cancer Research UK, said: ‘These researchers are not alone in trying to harness the body’s immune system to fight cancer – it’s a key area of research interest around the world.
‘This study is interesting, but a long way from a vaccine for cancer patients at the moment.& G, T, S, @  t1 M0 f# |! h# x
‘The next step is to see if this work can be repeated in human cells in the lab and then in larger trials with patients.’
Read more: http://www.dailymail.co.uk/healt ... .html#ixzz1slFejHuR' W4 N; C$ y  s. x  h' a
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                           第二篇：90%的癌症细胞披上了“糖衣”，而ImMucin撕开它们 2012年04月18日    - A/ Z" m% m% M$ F; b# x# R
据英国《每日邮报》近日报道，号称“万能疫苗”的ImMucin刚刚完成了临床实验，成绩相当不错：3位参与实验的血癌病人经治疗后痊愈。这次实验让人们对ImMucin更多了一分期待。  i5 z7 ?& i4 M. {' h5 S
这款治疗性疫苗由以色列韦克希尔生物疗法公司、特拉维夫大学的研究人员联合研制，实验在耶路撒冷的哈达沙医学中心进行，10位罹患多发性骨髓癌（血癌的一种）的患者接受了治疗。最后，共有7位病人完成了全部疗程，他们对癌细胞的免疫力相比治疗前都有明显提高，其中3位病人身上的癌细胞完全消失。治疗过程中没有发现任何副作用。/ ^" w; @7 G1 s
“我们对注射了2到4剂ImMucin疫苗的病人进行观察，发现它在病人的免疫系统中产生一种强劲、独特的反应。我们在一些病人身上观察到了初步的临床效果。”韦克希尔生物疗法公司称。
实验结果显示，除了可以治疗血癌，ImMucin还能用来对付乳腺癌、胰腺癌、前列腺癌、肠癌与卵巢癌等绝大多数癌症，因为它采取的策略，是锁定一种存在于90%癌细胞中的分子。即便是高效药物无能为力的癌症病例，例如抗癌“万灵药”郝塞汀都搞不定的乳腺癌，在施用“万能疫苗”后也收到了不错的疗效。ImMucin的另外一大优势是绝不动普通细胞一根毫毛，而大多数抗癌药在杀灭癌细胞的同时，也会多多少少地伤害正常细胞。) _0 n+ i; Q* s2 D, Z" j5 l
人体免疫系统会自动攻击细菌等外来细胞，但癌细胞出自患者自身，所以通常能轻松避开免疫系统。目前市场上流行的多数抗癌药物，也因癌细胞本身是能够无限生长、转化和转移的“不死军队”，而造成效果不佳。相比之下，ImMucin的原理简单却十分高明：激活人体内的天然抗癌大军——作用范围覆盖全身的免疫系统。
为了躲避追杀，肿瘤细胞学会了利用表面的糖分子掩饰自己，这层伪装令免疫系统将其看作正常细胞。而ImMucin的杀手锏就是让免疫系统分辨出“糖衣”。长期研究发现，糖衣位于MUC1蛋白的表面。破坏这种蛋白，其上的“糖衣”也会跟着土崩瓦解。人体中90%的癌症能产生这种蛋白，这意味着只要对付得了这种蛋白，就能克制绝大多数癌症。5 G# K0 l$ l, x( c! i  M
为了唤醒人体免疫系统，研究人员对疫苗结构进行了精心设计。ImMucin包含MUC1蛋白的全部信号肽区域，共含有21个碱基。这种设计有意模仿MUC1的功能性部分，目的是唤起人体免疫系统对MUC1的敌意，并留下长期记忆。激活免疫系统后，一旦发现癌细胞，大量抗体就会包围过来，直到目标被歼灭。这种利用免疫系统识别癌细胞的方法，能有效分别癌细胞与正常细胞。
如果一切进展顺利，ImMucin可能在2020年进入市场。
参考资料：! C( I: j* J' N; [7 b) r
ImMucin被称作治疗性疫苗，它的长项是治愈癌症，而不是预防。
一说起疫苗，人们想到的往往都是预防疾病。其实不然，按照作用类型区分，普通疫苗可以分为两种：预防性疫苗与治疗性疫苗，其中第一种占疫苗的绝大部分。我们最熟悉的狂犬病疫苗、乙肝疫苗、骨髓灰质炎疫苗等都属于第一类。一般人对治疗性疫苗接触不多，并且容易与药物相混淆。
               每日邮报连接：'Universal' vaccine that could beat 90 per cent of cancers is tested on humans for first time 5 L* d; l: I. x3 l0 i
A vaccine that targets a molecule in 90 per cent of all cancers has been tested on humans for the first time.9 r8 V, Q2 ~. Q$ O  H! C
Results from the safety trial - on patients with blood cancer - found all had greater immunity to the disease after receiving the vaccine. Three of the seven patients who have completed the treatment are now free of the condition.
As a therapeutic vaccine it is designed to be given to patients to help their bodies fight cancer rather than the majority - known as prophylactic vaccines - that aim to prevent disease in the first place. ( d  d2 y$ [& {) P- N
Researchers believe the jab could also tackle breast, prostate, pancreatic, bowel and ovarian cancers.
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Even tumours that resist treatment with the best medicines on the market, including the breast cancer ‘wonder drug’ Herceptin, may be susceptible to the vaccine.
If all goes well, the vaccine – called ImMucin – could be on the market by 2020.
More than 300,000 cases of cancer are diagnosed in Britain each year and the disease kills around half this number annually.4 q4 d4 A' Q4 ~, ~

Rather than attacking cancer cells, like many drugs, the new treatment harnesses the power of the immune system to fight tumours., n3 h, B# X- d$ V# D2 z! X% A# ~
The search for cancer vaccines has until now been hampered by fears that healthy tissue would be destroyed with tumours.1 Q# ^5 P+ J' a' O

Researchers from the drug company Vaxil Biotheraputics and Tel Aviv University have focused on a protein called MUC1 that is made in bigger amounts in cancerous cells than in healthy ones.) J8 [; E$ q; F2 t* L7 J. K' T
Not only is there more of it, but a sugar that it is ‘decorated’ with has a  distinctive shape. , L5 i, j) Z; U7 G1 |
The vaccine ‘trains’ the immune system to recognise the rogue sugar and turn its arsenal against the cancer.
The misshaped MUC1 sugar is found in 90 per cent of all cancers. There have been ‘dramatic’ results in tests on mice with breast tumours.
Now, Vaxil Biotheraputics have announced promising results in a human safety trial.
Ten patients suffering from multiple myeloma, a form of blood cancer, have now received the vaccine received the vaccine at the Hadassah Medical Centre in Jerusalem.. y' l8 `, f: [! ~% U4 g$ c
Seven of the patients have finished the treatment and Vaxil reported that all of them had greater immunity against cancer cells compared to before they were given the vaccine. Of the seven, three patients are reportedly free of detectable cancer.# y/ Y' [. x" ^- R( Q/ D
None of them have reported suffering side-effects apart from minor irritation.7 o3 m7 M7 A2 q- @+ U

A statement from Vaxil Biotheraputics said: 'ImMucin generated a robust and specific immune response in all patients which was observed after only 2-4 doses of the vaccine out of a maximum of 12 doses.
'In some of the patients, preliminary signs of clinical efficacy were observed.' 5 K7 I- q7 {$ x* w  @. a' Q
Years of large-scale human trials will be needed before the drug is judged safe and effective for widespread use in hospitals.
It could then be used with existing drugs to boost treatment and given to prevent tumours from coming back after surgery.2 A. i) h, Q7 J/ B. Y
Men and women known to be at high risk of cancer because of their genes could also be vaccinated in an attempt to stop tumours from appearing.7 F( T  P0 {1 S) x/ h' e$ z. X+ m
Dr Caitlin Palframan, of Breakthrough Breast Cancer, said: ‘This exciting  new approach could lead to treatments for breast cancer patients who have few options./ @+ [# ~. D9 L6 S
‘It also opens up the possibility of vaccinating high-risk women against breast cancer in the future.'

Read more: http://www.dailymail.co.uk/healt ... .html#ixzz1skzBvYVA

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